B-cell MalignanciesPhase 1/2NCT00983619
A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies
A Phase 1/2 study testing MEDI-551 and Rituximab in people with B-cell Malignancies and Cancer, run by MedImmune LLC at 21 sites in 5 countries.
Trial summary
The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- B-cell Malignancies, Cancer
- What is being tested?
- MEDI-551 and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 16 Apr 2010to 21 Mar 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed CLL, DLBCL, FL, or MM;
- Karnofsky Performance Status >= 70;
- Life expectancy of >= 12 weeks;
- Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
- Adequate hematological function
- Adequate organ function
Who cannot join
- Any available standard line of therapy known to be life-prolonging or life-saving;
- No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer
- Previous therapy directed against CD19
- Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;
- History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;
- Active infection requiring treatment
Show all 14Show fewer
- Autologous stem cell transplantation within 4 months prior to study entry;
- Allogeneic stem cell transplantation or any other organ transplant;
- Ongoing >= Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria.
- Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551;
- Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted);
- Documented current central nervous system involvement by leukemia or lymphoma;
- Pregnancy or lactation;
- Clinically significant abnormality on ECG.
Trial locations and contacts
21 sites in 5 countries.
21 sites in 5 countries
United States13 sites
Research Site
Birmingham, Alabama, 35249
Research Site
Chicago, Illinois, 60612
Research Site
Hershey, Pennsylvania, 17033
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Lake Success, New York, 11042
Research Site
Milwaukee, Wisconsin, 53226
Research Site
Morgantown, West Virginia, 26506
Research Site
New Brunswick, New Jersey, 08903
Research Site
Rochester, Minnesota, 55905
Research Site
Tampa, Florida, 33612
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Westwood, Kansas, 66205
Belgium3 sites
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Yvoir, 5530
About this study
Official title: A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies
The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).
Read the detailed description
To determine the MTD or OBD of MEDI-551 in participants with relapsed or refractory advanced B-cell malignancies.
- Conditions
- B-cell Malignancies, Cancer
- Being tested
- MEDI-551, Rituximab
- Keywords
- Cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI-551Drug
MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
RituximabDrug
Rituximab will be administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.
| Study group | Role | What they receive |
|---|---|---|
| Part A-MEDI-551 0.5 mg/kg | Experimental | Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part A-MEDI-551 1 mg/kg | Experimental | Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part A-MEDI-551 2 mg/kg | Experimental | Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part A-MEDI-551 4 mg/kg | Experimental | Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part A-MEDI-551 8 mg/kg | Experimental | Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part A-MEDI-551 12 mg/kg | Experimental | Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part B-MEDI-551 6 mg/kg | Experimental | Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part B-MEDI-551 12 mg/kg | Experimental | Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part B-MEDI-551 24 mg/kg | Experimental | Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. Receives: Drug: MEDI-551 |
| Part C-MEDI-551 8 mg/kg + rituximab | Experimental | Participants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. Receives: Drug: MEDI-551; Drug: Rituximab |
| Part C-MEDI-551 12 mg/kg + rituximab | Experimental | Participants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. Receives: Drug: MEDI-551; Drug: Rituximab |
| Part D-MEDI-551 12 mg/kg | Experimental | Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent. Receives: Drug: MEDI-551 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal Biologic Dose of MEDI-551 for Part A
Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.
Measured: Day 1 to Day 28 of Cycle 1
Highest Protocol-defined Dose for Part B
Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Measured: Day 1 to Day 28 of Cycle 1
Highest Protocol-defined Dose for Part C
Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Measured: Day 1 to Day 28 of Cycle 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C
A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,>= Grade 3 or 4 lymphopenia or leukopenia, <= Grade 4 neutropenia, <= Grade 4 thrombocytopenia, <= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.
Measured: Day 1 to Day 28 of Cycle 1
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Percentage of Participants With Complete Response for Part B, Part C, and Part D
Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Partial Response for Part B, Part C, and Part D
The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Complete Response for Part B, Part C, and Part D
Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D
Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Objective Response for Part B, Part C, and Part D
Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Measured: Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D
Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Disease Control for Part B, Part C, and Part D
Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Time to Response for Part B, Part C, and Part D
Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Progression Free Survival for Part B, Part C, and Part D
Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Overall Survival for Part B, Part C, and Part D
Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Secondary outcomes (23)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Measured: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Percentage of Participants With Complete Response for Part A
The CR is defined as disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Partial Response for Part A
The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Complete Response for Part A
Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Objective Response Rate for Part A
The ORR is defined as proportion of participants with CR or PR according to IWG criteria. CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Objective Response for Part A
The DOR is the first documentation of objective response to the first documented PD or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Disease Control Rate for Part A
Disease control includes CR, PR, or SD for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG -avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Disease Control for Part A
Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Time to Response for Part A
The TTR is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Progression Free Survival for Part A
The PFS is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. Kaplan-Meier method was used to evaluate PFS. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Overall Survival for Part A
The OS is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
Measured: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Trough Serum Concentration of MEDI-551 by Treatment Cycle
Trough serum concentration (Ctrough) is defined as lowest concentration reached by a drug before the next dose is administered. The Ctrough concentration of MEDI-551 by treatment cycle is reported.
Measured: For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
Peak Serum Concentration of MEDI-551 by Treatment Cycle
Peak serum concentration is concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose.
Measured: For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551
Area under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported.
Measured: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Apparent Clearance of MEDI-551
Apparent clearance of MEDI-551 is reported.
Measured: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Volume of Distribution of MEDI-551
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Central volume of distribution (Vd1) is defined as hypothetical volume into which a drug initially distributes upon administration and peripheral volume of distribution (Vd2) is defined as the sum of all tissue spaces outside the central compartment.
Measured: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Terminal Half-life (t1/2) of MEDI-551
Terminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase.
Measured: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551
Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported.
Measured: Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)
B-cell Concentration in Serum
B-cell Concentration in serum is reported.
Measured: Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)
Immunoglobulin (Ig) Concentration in Serum
Immunoglobin (Ig) concentration in serum is reported.
Measured: Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study start16 Apr 2010
- Primary completion21 Mar 2019
- Study completion21 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for B-cell MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medimmune Inc. Clinical Development, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983619
- Sponsor's protocol ID
- MI-CP204
- Other IDs
- 2009-016378-34, 2009
- Status last verified
- Apr 2020
- First submitted
- 22 Sep 2009
- Last updated
- 13 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies
- ClinicalTrials.gov ID
- NCT00983619
- Acronym / sponsor ID
- MI-CP204
- Conditions
- B-cell Malignancies, Cancer
- Keywords
- Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 16 Apr 2010 (actual)
- Primary completion
- 21 Mar 2019 (actual)
- Study completion
- 21 Mar 2019 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 13 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).
Detailed description
To determine the MTD or OBD of MEDI-551 in participants with relapsed or refractory advanced B-cell malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Part A-MEDI-551 0.5 mg/kg | Experimental | Drug: MEDI-551Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 1 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 2 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 4 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 8 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 12 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 6 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 12 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 24 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part C-MEDI-551 8 mg/kg + rituximab | Experimental | Drug: MEDI-551, Drug: RituximabParticipants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. |
| Part C-MEDI-551 12 mg/kg + rituximab | Experimental | Drug: MEDI-551, Drug: RituximabParticipants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. |
| Part D-MEDI-551 12 mg/kg | Experimental | Drug: MEDI-551Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed CLL, DLBCL, FL, or MM;
- Karnofsky Performance Status >= 70;
- Life expectancy of >= 12 weeks;
- Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
- Adequate hematological function
Key exclusion criteria (14 listed)
- Any available standard line of therapy known to be life-prolonging or life-saving;
- No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer
- Previous therapy directed against CD19
- Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;
- History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI-551MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. | Drug | Part A-MEDI-551 0.5 mg/kg, Part A-MEDI-551 1 mg/kg, Part A-MEDI-551 12 mg/kg, Part A-MEDI-551 2 mg/kg, Part A-MEDI-551 4 mg/kg, Part A-MEDI-551 8 mg/kg, Part B-MEDI-551 12 mg/kg, Part B-MEDI-551 24 mg/kg, Part B-MEDI-551 6 mg/kg, Part C-MEDI-551 12 mg/kg + rituximab, Part C-MEDI-551 8 mg/kg + rituximab, Part D-MEDI-551 12 mg/kg |
| RituximabRituximab will be administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. | Drug | Part C-MEDI-551 12 mg/kg + rituximab, Part C-MEDI-551 8 mg/kg + rituximab |
Primary outcome
Optimal Biologic Dose of MEDI-551 for Part A
Time frame: Day 1 to Day 28 of Cycle 1
Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.
Highest Protocol-defined Dose for Part B
Time frame: Day 1 to Day 28 of Cycle 1
Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Highest Protocol-defined Dose for Part C
Time frame: Day 1 to Day 28 of Cycle 1
Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C
Time frame: Day 1 to Day 28 of Cycle 1
A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,>= Grade 3 or 4 lymphopenia or leukopenia, <= Grade 4 neutropenia, <= Grade 4 thrombocytopenia, <= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Percentage of Participants With Complete Response for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.
Percentage of Participants With Partial Response for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Duration of Complete Response for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Duration of Objective Response for Part B, Part C, and Part D
Time frame: Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Duration of Disease Control for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Time to Response for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Progression Free Survival for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.
Overall Survival for Part B, Part C, and Part D
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
23 secondary outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D
Time frame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Percentage of Participants With Complete Response for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Partial Response for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Complete Response for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Objective Response Rate for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Objective Response for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Percentage of Participants With Disease Control Rate for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Duration of Disease Control for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Time to Response for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Progression Free Survival for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Overall Survival for Part A
Time frame: Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
Trough Serum Concentration of MEDI-551 by Treatment Cycle
Time frame: For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
Peak Serum Concentration of MEDI-551 by Treatment Cycle
Time frame: For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551
Time frame: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Apparent Clearance of MEDI-551
Time frame: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Volume of Distribution of MEDI-551
Time frame: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Terminal Half-life (t1/2) of MEDI-551
Time frame: Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551
Time frame: Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)
B-cell Concentration in Serum
Time frame: Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)
Immunoglobulin (Ig) Concentration in Serum
Time frame: Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Click here and search for drug information provided by the FDA.Link provided by the sponsor.
- Click here to find results for studies related to marketed products.Link provided by the sponsor.
- Statistical Analysis Plan (SAP)Link provided by the sponsor.
- MI-CP204 redacted CSPLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medimmune Inc. Clinical Development study director
MedImmune LLC
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MEDI-551 and Rituximab in people with B-cell Malignancies and Cancer, run by MedImmune LLC at 21 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Belgium, Italy, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal Biologic Dose of MEDI-551 for Part A (time frame: Day 1 to Day 28 of Cycle 1). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2020.