Clinical Trials /

Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)

NCT01891981

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Phase I/II Study of Moxetumomab

Title

  • Brief Title: Phase I/II Study of Moxetumomab
  • Official Title: Phase I/II Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
  • Clinical Trial IDs

    NCT ID: NCT01891981

    ORG ID: 2012-1143

    NCI ID: NCI-2013-02207

    Trial Conditions

    Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Moxetumomab Pasudotox Moxetumomab Pasudotox

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Moxetumomab Pasudotox Experimental Phase I Starting Dose: 30 g/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. Moxetumomab Pasudotox

    Eligibility Criteria

    Inclusion Criteria:

    1. 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.

    2. ECOG Performance status 0-2.

    3. Adequate liver function (bilirubin less than or equal to 1.5 mg/dL and SGPT or 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

    4. Provision of written informed consent.

    Exclusion Criteria:

    1. Patient with active heart disease (NYHA class greater than or equal to 2 as assessed
    by history and physical examination).

    2. Patients with a cardiac ejection fraction (as measured by either MUGA or
    echocardiogram) less than 40%

    3. Patients with active hepatitis

    4. 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.

    5. prior radioimmunotherapy within 3 years of enrollment

    6. serum albumin less than 2g/dL

    7. oxygen saturation at rest by pulse oximetry less than 88% or PaO2 less than or equal
    to 55mm Hg

    8. history of microangiopathic hemolysis, TTP or HUS.

    9. symptomatic CNS involvement

    10. Less than 100 days post -transplant or any evidence of active GVHD

    11. 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

    12. monoclonal antibody therapy less than 1 month

    13. 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

    14. HIV+/AIDS

    15. history of exposure to pseudomonas exotoxin containing molecule

    16. Patients with active lung infection or active pulmonary edema.

    17. 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.

    18. Patients with clinically significant ophthalmologic findings (as determined by an
    ophthalmologist) during screening should be excluded from the trial

    19. Pre-treatment greater than QTc interval of 490 ms

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD) of Moxetumomab

    Secondary Outcome Measures

    Overall Response Rate

    Trial Keywords

    Leukemia

    Acute Lymphoblastic Leukemia

    ALL

    Relapsed and/or refractory

    Moxetumomab Pasudotox

    Maximum tolerated dose

    MTD