Leukaemia, Lymphocytic, ChronicPhase 2NCT01077622
A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia
A Phase 2 study testing ofatumumab 100 mg, 1000 mg / vial in people with Leukaemia, Lymphocytic, Chronic, run by GlaxoSmithKline at 7 sites in 2 countries.
Trial summary
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Leukaemia, Lymphocytic, Chronic
- What is being tested?
- ofatumumab 100 mg, 1000 mg / vial
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 1 Sep 2009to 1 Apr 2011
- Phase
- Phase 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects eligible for enrolment in the study must meet all of the following criteria at the time of screening:
- Patients who gave consent to this study participation and signed into informed consent form.
- Previously treated(Patients who received at least one prior CLL therapy and have either relapsed or have refractory disease, both requiring therapy.) CLL with at least 5 x 109 B lymphocytes/ L (5000/μL). The diagnosis of CLL requires CD5, CD19, CD20 and CD23 positivity, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines [Hallek, 2008].
- Laboratory test values meet the following criteria which indicate that patients have sufficient physiological functions;
- Neutrophils:1≥ 500 /mm3 ALT ≤ 2.5 times upper local normal limit Creatinine ≤ 1.5 times upper local normal limit Total bilirubin≤ 1.5 times upper local normal limit
- 1:Patients should not receive any hematopoietic cytokine such as G-CSF preparations within 1 week before screening laboratory test for neutrophil counting.
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- Patients who passed the following periods from the last anti-cancer treatments at the time of screening: At least 4 weeks after anti-cancer chemotherapy. At least 4 weeks after anti-cancer radiotherapy. At least 4 weeks after glucocorticoids treatment for CLL unless ≤ 10 mg of prednisolone /day.
- At least 12 weeks after radio-immunotherapy and/or antibody therapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
- Life expectancy more than 24 weeks after screening test.
- Aged ≥ 20 (at the time of signing informed consent).
- Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day).
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria is met:
- Active malignancy which needs therapy with anti-cancer drug, except for CLL.
- Known Richter's transformation.
- Previous autologous stem cell transplantation, within 24 weeks prior to screening.
- Previous allogenic stem cell transplantation.
- Known CNS involvement.
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- History of significant cerebrovascular disease.
- Current cardiac disease requiring medical treatment (e.g. atrial flutter treated with acetylsalicylic acid and beta blocking agents).
- Chronic or active infectious disease requiring systemic (intravenous or oral) treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
- Suspected/known immediate or delayed hypersensitivity to components of ofatumumab.
- Patients previously treated with ofatumumab.
- Positive serology test for any of HBsAg, anti-HBcAb or anti-HCVAb. If only anti-HBcAb results is positive, HBV-DNA test will be performed. If HBV-DNA results in negative, the patient is eligible.
- HIV positivity.
- Pregnant or lactating women.
- Women of childbearing potential not willing to use adequate contraception during the study and one year after the last dose of ofatumumab, and male patients not willing to use adequate contraception during the study. Adequate contraception is defined as follows but not limited to; Abstinence. Oral Contraceptive (exclude oral progesterone alone). Intrauterine device (IUD) or intrauterine system (IUS). Male partner sterilization. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (gel / film) etc.
- Use of an investigational drug within 4 weeks prior to screening.
- Current participation in any other clinical study.
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
- Patients who an investigator (or sub investigator) judges ineligible to this study.
- Note; Child-bearing potential: a woman with functioning ovaries and uterine, or no documented sterility (i.e., a woman with functioning ovaries who have a current documented tubal ligation, women who have had a hysterectomy, women who are post-menopausal, or women who have had both ovaries surgically removed).
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Japan5 sites
GSK Investigational Site
Aichi, 466-8650
GSK Investigational Site
Kanagawa, 259-1143
GSK Investigational Site
Nagasaki, 852-8501
GSK Investigational Site
Tokyo, 104-0045
GSK Investigational Site
Tokyo, 135-8550
South Korea2 sites
GSK Investigational Site
Seoul, 110-744
GSK Investigational Site
Seoul, 138-736
About this study
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Read more
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
Read the detailed description
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
- Conditions
- Leukaemia, Lymphocytic, Chronic
- Being tested
- ofatumumab 100 mg, 1000 mg / vial
- Medical subject headings
- Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ofatumumab 100 mg, 1000 mg / vialDrug
ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg
| Study group | Role | What they receive |
|---|---|---|
| 2000 mg dose | Experimental | ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg Receives: Drug: ofatumumab 100 mg, 1000 mg / vial |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Dose-limiting Toxicity (DLT)
A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) >=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as >= G3 until the next day); and any of following: >= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia).
Measured: Up to Week 8
Percentage of Participants (Par.) With Objective Response (OR), Defined as Complete Remission (CR), CR Incomplete (CRi), Partial Remission (PR), and Nodular PR (nPR) as Assessed by a Safety and Evaluation Review Committee (SERC) and the Investigator
Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils >=1.5*10^9/liter (L), platelets >100*10^9/L, hemoglobin >11.0 grams/deciliter, lymphocytes (LC) <4.0*10^9/L, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM.
Measured: Up to Week 48
Secondary outcomes (40)
Progression-free Survival (PFS) as Assessed by a SERC
PFS is defined as the time from the start of treatment to the first documented sign of progressive disease (PD) or death due to any cause (whichever occurs earlier).
Measured: Up to Week 48
Duration of Response as Assessed by a SERC
Duration of response is defined as the time from the first documented evidence of PR or better until the first documented sign of PD or death due to any reason in participants with PR or better.
Measured: Up to Week 48
Overall Survival
Overall survival is defined as the time from the first infusion of investigational drug to death due to any cause.
Measured: Up to Week 48
Time to Response as Assessed by a SERC
Time to response is defined as the time from the first infusion of investigational drug to the first response (PR or better).
Measured: Up to Week 48
Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC
Time to next CLL therapy is defined as the time from the first infusion of investigational drug to the first administration of the next CLL treatment. CLL therapy includes anti-cancer chemotherapy, anti-cancer radiotherapy, radio-immunotherapy, and antibody therapy.
Measured: Up to Week 48
Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator
Blood samples of the participants were collected for the assessment of hemoglobin.
Measured: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator
Blood samples of the participants were collected for the assessment of lymphocytes.
Measured: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator
Bone marrow (BM) aspiration was performed, and the bone marrow smears were prepared for the assessment of lymphocytes in the BM.
Measured: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator
Blood samples of the participants were collected for the assessment of total neutrophils.
Measured: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator
Blood samples of the participants were collected for the assessment of platelets.
Measured: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC
SERC assessed bone marrow infiltration with the bone marrow smears of participants provided by trial sites.
Measured: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC
SERC assessed lymphocytes based on the data provided by trial sites.
Measured: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC
SERC assessed lymphocytes in the bone marrow (BM) based on the data with BM smears provided by trial sites.
Measured: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC
SERC assessed total neutrophils based on the data provided by trial sites.
Measured: Weeks 8, 16, 24, 36, and 48
Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells
CD19+ CD20+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD20+ CD23+ Cells
CD20+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD19+ CD23+ Cells
CD19+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD19+ CD5+ Cells
CD19+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD20+ CD5+ Cells
CD20+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD23+ CD5+ Cells
CD23+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda
Peripheral blood Ig kappa and Ig lambda were measured using flow cytometry. Abnormality of a ratio of Ig kappa and Ig lambda indicates clonality of lymphocytes. A normal range of this parameter is between 1.0 and 3.2.
Measured: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks
Night sweats are one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had night sweats at BL, and still had night sweats at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had night sweats at BL, but did not have night sweats at Week 1 are represented in the BL, yes; Week 1, no category.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks
Weight loss is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had weight loss at BL, and still had weight loss at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had weight loss at BL, but did not have weight loss at Week 1 are represented in the BL, yes; Week 1, no category.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks
Fever is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had fever at BL, and still had fever at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had fever at BL, but did not have fever at Week 1 are represented in the BL, yes; Week 1, no category.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks
Extreme fatigue is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had extreme fatigue at BL, and still had extreme fatigue at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had extreme fatigue at BL, but did not have extreme fatigue at Week 1 are represented in the BL, yes; Week 1, no category.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48
Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants.
Measured: Baseline and Weeks 8, 24, and 48
Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48
HAHA are indicators of immunogenicity to ofatumumab.
Measured: Screening; Weeks 24 and 48
Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
ECOG PS is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. The grades for the scale range from 0 (fully active) to 4 (completely disabled), with increasing severity.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab
Blood sampling on Day 1 and at Weeks 7 and 24 for pharmacokinetic (PK) evaluation was performed at the following time points: 0.5 hour (hr) before infusion; end of infusion; and 10 minutes (min), 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Minimum Plasma Concentration (Cmin) of Ofatumumab
Blood sampling at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
Measured: Weeks 7 and 24
Time to Reach Cmax (Tmax) Following Ofatumumab Administration
Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Half-life (t1/2) of Ofatumumab
t1/2 of ofatumumab is the time required for the plasma concentration of ofatumumab to decrease by half. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab
AUC(0-t) was evaluated from the plasma concentration versus time curve from time zero to the last measurable time point (time t). Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7
Blood sampling at Week 7 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
Measured: Week 7
Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24
Blood sampling at Week 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
Measured: Week 24
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab
Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Clearance (CL) of Ofatumumab From Plasma
CL of ofatumumab from plasma of participants was evaluated. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab
Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Volume of Distribution at Steady State (Vss) for Ofatumumab
Vss for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body in equilibrium conditions to steady-state plasma concentrations. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Mean Residence Time (MRTinf) of Ofatumumab
MRTinf is the average amount of time that ofatumumab spends in the body. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Measured: Day 1; Weeks 7 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2010 (estimated)
- Study start1 Sep 2009
- Primary completion1 Apr 2011
- Study completion1 Apr 2011
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 Leukaemia, Lymphocytic, ChronicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01077622
- Sponsor's protocol ID
- 112758
- Status last verified
- Oct 2013
- First submitted
- 25 Feb 2010
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01077622
- Acronym / sponsor ID
- 112758
- Conditions
- Leukaemia, Lymphocytic, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Sep 2009
- Primary completion
- 1 Apr 2011 (actual)
- Study completion
- 1 Apr 2011 (actual)
- First posted
- 1 Mar 2010 (estimated)
- Results
- Posted 27 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
Detailed description
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2000 mg dose | Experimental | Drug: ofatumumab 100 mg, 1000 mg / vialofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects eligible for enrolment in the study must meet all of the following criteria at the time of screening:
- Patients who gave consent to this study participation and signed into informed consent form.
- Previously treated(Patients who received at least one prior CLL therapy and have either relapsed or have refractory disease, both requiring therapy.) CLL with at least 5 x 109 B lymphocytes/ L (5000/μL). The diagnosis of CLL requires CD5, CD19, CD20 and CD23 positivity, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines [Hallek, 2008].
- Laboratory test values meet the following criteria which indicate that patients have sufficient physiological functions;
- Neutrophils:1≥ 500 /mm3 ALT ≤ 2.5 times upper local normal limit Creatinine ≤ 1.5 times upper local normal limit Total bilirubin≤ 1.5 times upper local normal limit
Key exclusion criteria (20 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria is met:
- Active malignancy which needs therapy with anti-cancer drug, except for CLL.
- Known Richter's transformation.
- Previous autologous stem cell transplantation, within 24 weeks prior to screening.
- Previous allogenic stem cell transplantation.
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 |
|---|---|---|
| ofatumumab 100 mg, 1000 mg / vialofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg | Drug | 2000 mg dose |
Primary outcome
Number of Participants With a Dose-limiting Toxicity (DLT)
Time frame: Up to Week 8
A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) >=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as >= G3 until the next day); and any of following: >= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia).
Percentage of Participants (Par.) With Objective Response (OR), Defined as Complete Remission (CR), CR Incomplete (CRi), Partial Remission (PR), and Nodular PR (nPR) as Assessed by a Safety and Evaluation Review Committee (SERC) and the Investigator
Time frame: Up to Week 48
Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils >=1.5*10^9/liter (L), platelets >100*10^9/L, hemoglobin >11.0 grams/deciliter, lymphocytes (LC) <4.0*10^9/L, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM.
40 secondary outcomes
Progression-free Survival (PFS) as Assessed by a SERC
Time frame: Up to Week 48
Duration of Response as Assessed by a SERC
Time frame: Up to Week 48
Overall Survival
Time frame: Up to Week 48
Time to Response as Assessed by a SERC
Time frame: Up to Week 48
Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC
Time frame: Up to Week 48
Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator
Time frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator
Time frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator
Time frame: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator
Time frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator
Time frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC
Time frame: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC
Time frame: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC
Time frame: Weeks 8, 16, 24, 36, and 48
Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC
Time frame: Weeks 8, 16, 24, 36, and 48
Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD20+ CD23+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD19+ CD23+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD19+ CD5+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD20+ CD5+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Peripheral Blood CD23+ CD5+ Cells
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda
Time frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48
Time frame: Baseline and Weeks 8, 24, and 48
Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48
Time frame: Screening; Weeks 24 and 48
Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48
Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Minimum Plasma Concentration (Cmin) of Ofatumumab
Time frame: Weeks 7 and 24
Time to Reach Cmax (Tmax) Following Ofatumumab Administration
Time frame: Day 1; Weeks 7 and 24
Half-life (t1/2) of Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7
Time frame: Week 7
Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24
Time frame: Week 24
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Clearance (CL) of Ofatumumab From Plasma
Time frame: Day 1; Weeks 7 and 24
Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Volume of Distribution at Steady State (Vss) for Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Mean Residence Time (MRTinf) of Ofatumumab
Time frame: Day 1; Weeks 7 and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ofatumumab 100 mg, 1000 mg / vial in people with Leukaemia, Lymphocytic, Chronic, run by GlaxoSmithKline at 7 sites in 2 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 12 inclusion and 20 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 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Japan, South Korea. 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 phase mean?
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 27 Jan 2012). 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?
Number of Participants With a Dose-limiting Toxicity (DLT) (time frame: Up to Week 8). The study lists 2 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 30 May 2017.