LeukemiaPhase 1NCT01891981
Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
A Phase 1 study testing Moxetumomab Pasudotox in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of moxetumomab pasudotox that can be given to patients with relapsed and/or refractory ALL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Moxetumomab Pasudotox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2013to 12 Apr 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients age 18 years or older with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate, Pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
- Adequate liver function (bilirubin less than or equal to 1.5 mg/dL and serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) less than or equal 2.5 x upper limit of normal (ULN), unless considered due to tumor or hemolysis), and renal function ( Calculated CrCl of greater than or equal to 50 or serum creatinine less than 2 x ULN.) Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is less than or equal to 2.0 mg/dL (unless due to hemolysis or Gilbert's disease, i.e. mainly indirect bilirubin) and creatinine less than or equal 2 mg/dL
- Provision of written informed consent.
Who cannot join
- Patient with active heart disease (NYHA class greater than or equal to 2 as assessed by history and physical examination).
- Patients with a cardiac ejection fraction (as measured by either multigated radionuclide angiography (MUGA) or echocardiogram) less than 40%
- Patients with active hepatitis
- Pregnant or breast-feeding women. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of start of treatment.
- prior radioimmunotherapy within 3 years of enrollment
- serum albumin less than 2g/dL
Show all 19Show fewer
- oxygen saturation at rest by pulse oximetry less than 88% or PaO2 less than or equal to 55mm Hg
- history of microangiopathic hemolysis, TTP or HUS.
- symptomatic central nervous system (CNS) involvement
- Less than 100 days post -transplant or any evidence of active graft-versus-host disease (GVHD)
- systemic chemotherapy less than 14 days prior; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
- monoclonal antibody therapy less than 1 month
- investigational agents within 28 days of dosing; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
- HIV+/AIDS
- history of exposure to pseudomonas exotoxin containing molecule
- Patients with active lung infection or active pulmonary edema.
- Patients with laboratory findings consistent with Grade equal to greater than 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct.
- Patients with clinically significant ophthalmologic findings (as determined by an ophthalmologist) during screening should be excluded from the trial
- Pre-treatment greater than corrected QT interval (QTc) interval of 490 ms
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I/II Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
The goal of this clinical research study is to find the highest tolerable dose of moxetumomab pasudotox that can be given to patients with relapsed and/or refractory ALL.
Read the detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3-6 participants will be enrolled in the Phase 1 portion of the study.
If you are in Phase 1, the dose of moxetumomab pasudotox you receive will depend on when you join the study. The first group will receive the lowest dose level of moxetumomab pasudotox. Each additional group will receive a higher dose than the previous group, if no intolerable side effects were seen.
If you are in Phase 2, you will receive the highest dose of moxetumomab pasudotox found to be safe in the Phase 1 portion of the study.
Study Drug Administration:
You will receive moxetumomab pasudotox by vein on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. You may be treated in the hospital for the first cycle. If your doctor thinks it is needed, the length of study cycles may be changed.
You may receive drugs to control side effects one hour before your dose of the study drug and up to 12 hours after your dose of the study drug. You may also receive fluids for hydration before and after your dose of the study drug.
Study Visits:
Every week during Cycle 1, blood (about 1 tablespoon) will be drawn for routine tests.
Within 1 week before Day 1 of each study cycle:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If your doctor thinks it is needed, you will have an eye exam.
- Blood (about 2 teaspoons) will be drawn to test for drug antibodies.
On Day 1 (1st dose) of Cycle 1, before and right after your first dose of study drug and then 4-5 more times over the next 8 hours, blood (about 1/2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. At the 6th dose, blood (about 1/2 teaspoon each time) will be drawn before and right after your dose of study drug for PK testing. PK testing for the 1st and 6th dose will be repeated for Cycle 2 and every 4th treatment cycle until the end of treatment.
If the doctor thinks the disease is responding to the study drug, blood (about 1 tablespoon) will be drawn at least 1 time every week for routine tests.
Between Days 14-21 (+/- 7 days) of Cycle 1, you will have a bone marrow biopsy/aspiration. You will have additional bone marrow biopsy/aspirations every 2-4 cycles after that, and then every 3 months for up to 1 year during the follow-up period.
At the end of each cycle, urine will be collected for routine tests.
After your last dose of study drug, blood (about 2 teaspoons) will be drawn to test for drug antibodies.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. If your doctor thinks the disease is responding, you may receive up to 6 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
Follow-Up Visit:
About 30 days after the last dose of the study drug, you will be asked to return to the clinic for follow-up tests. During this visit, you may have blood drawn and other tests performed to check the status of the disease, to test for drug antibodies, and to check your health.
If you cannot come to MD Anderson, you will be contacted by phone and asked about your health.
This is an investigational study. Moxetumomab pasudotox is not FDA approved or commercially available. At this time, it is being used for research purposes only.
Up to 60 patients will take part in the study. All will be enrolled at MD Anderson.
- Conditions
- Leukemia
- Being tested
- Moxetumomab Pasudotox
- Keywords
- Leukemia, Acute Lymphoblastic Leukemia, ALL, Relapsed and/or refractory, Moxetumomab Pasudotox, Maximum tolerated dose, MTD
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moxetumomab PasudotoxDrug
Phase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle.
Phase II Starting Dose: Maximum tolerated dose from Phase I.
| Study group | Role | What they receive |
|---|---|---|
| Moxetumomab Pasudotox | Experimental | Phase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle.
Phase II Starting Dose: Maximum tolerated dose from Phase I. Receives: Drug: Moxetumomab Pasudotox |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Moxetumomab
Maximum tolerated dose defined as the highest dose level in which 6 patients have been evaluated for toxicity and fewer than 2 dose limiting toxicities (DLTs) were observed. A non-hematologic DLT defined as a clinically significant Grade 3 or 4 adverse event or abnormal laboratory value assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 21(+/- 2) days on study. A hematologic dose-limiting toxicity defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy.
Measured: After second 21 day cycle
Secondary outcomes (1)
Overall Response Rate
Primary efficacy outcome is overall response rate (including CR, CRi and PR). Complete remission (CR): Neutrophil count > 1.0 x109/L, platelet count >100x109/L, and normal marrow differential (< 5% blasts). Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recovery of counts (platelets < 100 x 109/L; neutrophils < 1 x 109/L). Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of > 50% and not more than 25% abnormal cells in the marrow. Kaplan and Meier product limit method used to estimate the event-free survival (EFS) and overall survival (OS) and a 95% confidence interval for the median EFS and OS provided. Univariate and multivariate Cox proportional hazards regression model used to identify prognostic factors for EFS and OS.
Measured: After second 21 day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2013 (estimated)
- Study start17 Dec 2013
- Primary completion12 Apr 2017
- Study completion12 Apr 2017
Why it stopped: Ph I Exempt as it did not proceed to the Phase II terminated early by the supporter
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- MedImmune LLC
- Responsible party
- Sponsor
- Investigators
- Farhad Ravandi-Kashani, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01891981
- Sponsor's protocol ID
- 2012-1143
- Other IDs
- NCI-2013-02207
- Status last verified
- Oct 2023
- First submitted
- 28 Jun 2013
- Last updated
- 13 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Muller F, Cunningham T, Stookey S, Tai CH, Burkett S, Jailwala P, Stetler Stevenson M, Cam MC, Wayne AS, Pastan I. 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1867-E1875. doi: 10.1073/pnas.1714512115. Epub 2018 Feb 5.
PubMed 29432154
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT01891981
- Acronym / sponsor ID
- 2012-1143
- Conditions
- Leukemia
- Keywords
- Leukemia, Acute Lymphoblastic Leukemia, ALL, Relapsed and/or refractory, Moxetumomab Pasudotox, Maximum tolerated dose, MTD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Ph I Exempt as it did not proceed to the Phase II terminated early by the supporter
- Enrolment
- 16 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- MedImmune LLC
- Study start
- 17 Dec 2013 (actual)
- Primary completion
- 12 Apr 2017 (actual)
- Study completion
- 12 Apr 2017 (actual)
- First posted
- 3 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find the highest tolerable dose of moxetumomab pasudotox that can be given to patients with relapsed and/or refractory ALL.
Detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3-6 participants will be enrolled in the Phase 1 portion of the study.
If you are in Phase 1, the dose of moxetumomab pasudotox you receive will depend on when you join the study. The first group will receive the lowest dose level of moxetumomab pasudotox. Each additional group will receive a higher dose than the previous group, if no intolerable side effects were seen.
If you are in Phase 2, you will receive the highest dose of moxetumomab pasudotox found to be safe in the Phase 1 portion of the study.
Study Drug Administration:
You will receive moxetumomab pasudotox by vein on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. You may be treated in the hospital for the first cycle. If your doctor thinks it is needed, the length of study cycles may be changed.
You may receive drugs to control side effects one hour before your dose of the study drug and up to 12 hours after your dose of the study drug. You may also receive fluids for hydration before and after your dose of the study drug.
Study Visits:
Every week during Cycle 1, blood (about 1 tablespoon) will be drawn for routine tests.
Within 1 week before Day 1 of each study cycle:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If your doctor thinks it is needed, you will have an eye exam.
- Blood (about 2 teaspoons) will be drawn to test for drug antibodies.
On Day 1 (1st dose) of Cycle 1, before and right after your first dose of study drug and then 4-5 more times over the next 8 hours, blood (about 1/2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. At the 6th dose, blood (about 1/2 teaspoon each time) will be drawn before and right after your dose of study drug for PK testing. PK testing for the 1st and 6th dose will be repeated for Cycle 2 and every 4th treatment cycle until the end of treatment.
If the doctor thinks the disease is responding to the study drug, blood (about 1 tablespoon) will be drawn at least 1 time every week for routine tests.
Between Days 14-21 (+/- 7 days) of Cycle 1, you will have a bone marrow biopsy/aspiration. You will have additional bone marrow biopsy/aspirations every 2-4 cycles after that, and then every 3 months for up to 1 year during the follow-up period.
At the end of each cycle, urine will be collected for routine tests.
After your last dose of study drug, blood (about 2 teaspoons) will be drawn to test for drug antibodies.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. If your doctor thinks the disease is responding, you may receive up to 6 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
Follow-Up Visit:
About 30 days after the last dose of the study drug, you will be asked to return to the clinic for follow-up tests. During this visit, you may have blood drawn and other tests performed to check the status of the disease, to test for drug antibodies, and to check your health.
If you cannot come to MD Anderson, you will be contacted by phone and asked about your health.
This is an investigational study. Moxetumomab pasudotox is not FDA approved or commercially available. At this time, it is being used for research purposes only.
Up to 60 patients will take part in the study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Moxetumomab Pasudotox | Experimental | Drug: Moxetumomab PasudotoxPhase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. Phase II Starting Dose: Maximum tolerated dose from Phase I. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients age 18 years or older with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate, Pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
- Adequate liver function (bilirubin less than or equal to 1.5 mg/dL and serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) less than or equal 2.5 x upper limit of normal (ULN), unless considered due to tumor or hemolysis), and renal function ( Calculated CrCl of greater than or equal to 50 or serum creatinine less than 2 x ULN.) Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is less than or equal to 2.0 mg/dL (unless due to hemolysis or Gilbert's disease, i.e. mainly indirect bilirubin) and creatinine less than or equal 2 mg/dL
- Provision of written informed consent.
Key exclusion criteria (19 listed)
- Patient with active heart disease (NYHA class greater than or equal to 2 as assessed by history and physical examination).
- Patients with a cardiac ejection fraction (as measured by either multigated radionuclide angiography (MUGA) or echocardiogram) less than 40%
- Patients with active hepatitis
- Pregnant or breast-feeding women. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of start of treatment.
- prior radioimmunotherapy within 3 years of enrollment
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 |
|---|---|---|
| Moxetumomab PasudotoxPhase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. Phase II Starting Dose: Maximum tolerated dose from Phase I. | Drug | Moxetumomab Pasudotox |
Primary outcome
Maximum Tolerated Dose (MTD) of Moxetumomab
Time frame: After second 21 day cycle
Maximum tolerated dose defined as the highest dose level in which 6 patients have been evaluated for toxicity and fewer than 2 dose limiting toxicities (DLTs) were observed. A non-hematologic DLT defined as a clinically significant Grade 3 or 4 adverse event or abnormal laboratory value assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 21(+/- 2) days on study. A hematologic dose-limiting toxicity defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy.
1 secondary outcome
Overall Response Rate
Time frame: After second 21 day cycle
Results and safety
The study was stopped early (reason given: Ph I Exempt as it did not proceed to the Phase II terminated early by the supporter). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Derived from this study: PubMed 29432154Muller F, Cunningham T, Stookey S, Tai CH, Burkett S, Jailwala P, Stetler Stevenson M, Cam MC, Wayne AS, Pastan I. 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1867-E1875. doi: 10.1073/pnas.1714512115. Epub 2018 Feb 5.
- University of Texas MD Anderson Cancer Center WebsiteLink 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.
Farhad Ravandi-Kashani, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Moxetumomab Pasudotox in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
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 4 inclusion and 19 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: stopped early, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Ph I Exempt as it did not proceed to the Phase II terminated early by the supporter). Results are not available in the source record.
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?
Maximum Tolerated Dose (MTD) of Moxetumomab (time frame: After second 21 day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01891981, which also lists 1 linked publication.
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 Oct 2023.