Clinical Trials /

Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)

NCT03207542

Description:

The goal of this clinical research study is to learn if daratumumab can help to control B- or T-cell acute lymphoblastic leukemia (ALL). The safety of daratumumab will also be studied. This is an investigational study. Daratumumab is FDA approved and commercially available for treatment of multiple myeloma. It is considered investigational to use daratumumab to treat ALL. The study doctor can explain how the study drug is designed to work. Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)
  • Official Title: An Open-label Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)

Clinical Trial IDs

  • ORG STUDY ID: 2016-0973
  • NCT ID: NCT03207542

Conditions

  • Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Interventions

DrugSynonymsArms
DaratumumabB-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Purpose

The goal of this clinical research study is to learn if daratumumab can help to control B- or T-cell acute lymphoblastic leukemia (ALL). The safety of daratumumab will also be studied.

Detailed Description

      Study Drug Administration:

      Each cycle is 28 days.

      If participant is found to be eligible to take part in this study, participant will receive
      daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and
      15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond. Participant's first dose of
      daratumumab will be given over about 7 hours.

      In this study, the following will be done to lower the chance of a daratumumab infusion
      related reaction:

        -  Participant will get medications, including steroids, acetaminophen, and/or
           antihistamine before the infusion. If participant is considered high risk, participant
           may also get medications, including inhaled steroids, after the infusion.

        -  The infusion may be slowed down or stopped if participant has a reaction.

        -  Participant may stay overnight in the hospital after the infusion so the study staff can
           check participant's health.

      Participant may ask the study staff for information about how these drugs are given and their
      risks. Participant may also be asked to stay in the hospital overnight to watch participant
      for side effects, if needed.

      Length of Study:

      Participant may receive daratumumab for up to 1 year. Participant will no longer be able to
      take the study drug if the disease gets worse, if intolerable side effects occur, or if
      participant is unable to follow study directions.

      Study Visits:

      Within 24 hours before participant's first dose of study drug, if participant can become
      pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.

      Every 2 weeks during Cycles 1-6, blood (about 1 teaspoon) will be drawn for CMV testing.

      On Day 1 of Cycles 1 and 2:

        -  Participant will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

        -  Blood (about 2 teaspoons) will be drawn for pharmacokinetic (PK) testing before
           participant's dose of study drug. Blood (about 1 teaspoon) for PK testing will also be
           drawn 2 times over the 2 hours after the dose. During Cycle 2, blood will only be drawn
           1 time after the dose. PK testing measures the amount of study drug in the body at
           different time points.

        -  During Cycle 1, blood (about 1 teaspoon) will be drawn for immune system testing.

        -  During Cycle 2, participant will have a bone marrow aspirate/biopsy to check the status
           of the disease.

      On Days 2 and 4 of Cycle 1, blood (about 1 teaspoon) will be drawn for PK testing.

      On Days 8, 15, 22 of Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine
      tests. On Day 8 of Cycle 1, blood (about 1 teaspoon) will be drawn before participant's dose
      of study drug for PK testing.

      Day 22 of Cycle 2, blood (about 1 teaspoon) will be drawn for PK testing before and after
      participant's dose of study drug.

      On Day 1 of Cycles 3-6:

        -  Participant will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

        -  During Cycle 3, participant will have an EKG.

        -  During Cycle 3, blood (about 1 teaspoon each time) will be drawn for PK testing before
           and after participant's dose of study drug.

        -  If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a
           pregnancy test.

      On Day 1 of Cycles 3 and beyond, participant will have a bone marrow biopsy/aspirate to check
      the status of the disease. If the disease appears to be responding to the study drug, the
      study doctor will decide how often participant will have this procedure.

      On Day 15 of Cycles 3-6, blood (about 2 teaspoons) will be drawn for routine tests.

      On Day 1 of Cycles 7 and beyond:

        -  Participant will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests and CMV testing.

        -  During Cycle 7 only, participant will have an EKG.

        -  During Cycles 7 and 12, blood (about 2 teaspoons) will be drawn for PK and immune system
           testing.

        -  If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a
           pregnancy test.

      While on study, if participant chooses to not have any of the PK blood draws, participation
      in this study will be over.

      End of Treatment:

      About 28-35 days after the last dose of daratumumab:

        -  Participant will have a physical exam.

        -  Participant will have an EKG.

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

        -  If the doctor thinks it is needed, participant may have a bone marrow biopsy/aspiration
           to check the status of the disease.

      Follow-Up Visits:

      The study staff will call participant to ask how participant is doing 1 time each month for
      the first year after participant's End-of-Treatment visit, then every 6 months during the
      second year after the visit, and then 1 time every year after that. Each call should last
      about 5 minutes.

      At 4 and 8 weeks after participant's last dose of study drug, blood (about 2 teaspoons) will
      be drawn for PK and immune system testing.

      At 30 and 60 days after participant's last dose of study drug and then every 2-3 months after
      that for 1 year:

        -  Participant will have a physical exam.

        -  If the disease appeared to be responding to the study drug, blood (about 2 teaspoons)
           will be drawn for routine tests. Every 4-12 weeks, this sample may be used for CMV
           testing. If the disease appears to get worse, participant will stop having these blood
           draws.

        -  If the disease appeared to be responding to the study drug, participant will have a bone
           marrow aspirate and/or biopsy.

        -  If the disease appeared to be responding to the study drug, participant will have an EKG
           at participant's first follow-up visit.

      After 1 year, participant may continue to have follow-up visits as part of participant's
      routine care. This will be discussed with participant by the study doctor in more detail.

      This is an investigational study. Daratumumab is FDA approved and commercially available for
      treatment of multiple myeloma. It is considered investigational to use daratumumab to treat
      ALL.

      The study doctor can explain how the study drug is designed to work.

      Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)ExperimentalParticipants receive Daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond. Each cycle is 28 days.
  • Daratumumab
T-Cell Precursor Acute Lymphoblastic Leukemia (ALL)ExperimentalParticipants receive Daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond. Each cycle is 28 days.
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          1. Subject must be at least 18 years of age.

          2. The subject must have precursor B-cell or T-cell acute lymphoblastic leukemia. B-cell:
             relapsed or refractory after first or subsequent salvage therapy; or T-cell: relapsed
             or refractory with first remission duration less than or equal to 12 months in first
             salvage; or relapsed or refractory after first or subsequent salvage therapy.

          3. More than 5% blasts in bone marrow.

          4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          5. Life expectancy of >/= 12 weeks.

          6. Women of childbearing potential must commit to either abstain continuously from
             heterosexual sexual intercourse or to use 2 methods of reliable birth control
             simultaneously. This includes one highly effective form of contraception (tubal
             ligation, intrauterine device, hormonal [birth control pills, injections, hormonal
             patches, vaginal rings or implants] or partner's vasectomy) and one additional
             effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical
             cap). Contraception must begin prior to dosing. Reliable contraception is indicated
             even where there has been a history of infertility, unless due to hysterectomy or
             bilateral oophorectomy. A man who is sexually active with a woman of childbearing
             potential must always use a latex or synthetic condom during the study and for 4
             months after discontinuing daratumumab.

          7. A woman of childbearing potential must have a negative serum or urine pregnancy test
             at screening within 14 days and again within 72 hours prior to dosing.

          8. Each subject must sign an informed consent form (ICF) indicating that he or she
             understands the purpose of and procedures required for the study and are willing to
             participate in the study. Subjects must be willing and able to adhere to the
             prohibitions and restrictions specified in this protocol, as referenced in the ICF.

        Exclusion Criteria:

          1. Active leukemic central nervous system (CNS) disease.

          2. Active acute Graft-versus-Host Disease (GvHD) or chronic GVHD grade 2 or higher.

          3. Patients who have received prior stem cell transplantation will be allowed to enroll
             as long as prior transplantation has been at least 3 months before enrollment in the
             trial and any transplant related toxicities have subsided to Grade 1 or less.

          4. Philadelphia chromosome-positive (Ph+) ALL.

          5. Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (steroid or
             hydroxyurea can be used up to 24 hours prior to first daratumumab infusion for control
             of high white cell counts)

          6. Cancer immunotherapy within four weeks prior to start of daratumumab treatment
             (exception blinatumomab within two weeks prior)

          7. Diagnosed or treated for malignancy other than ALL, except: 1) Malignancy treated with
             curative intent and with no known active disease present for >/= 3 years before
             treatment; 2) Adequately treated non-melanoma skin cancer or lentigo maligna or
             carcinoma in situ (e.g. cervical, breast) without evidence of disease; 3) or
             malignancy that in the opinion of the investigator, with concurrence with the MDACC
             IND office, is considered cured with minimal risk of recurrence within 3 years.

          8. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced
             Expiratory Volume in 1 second (FEV1) <50% of predicted normal. NOTE: FEV1 testing is
             required for patients suspected of having COPD and subjects must be excluded if FEV1
             <50% of predicted normal.

          9. Subject has known moderate or severe persistent asthma within the past 2 years (see
             Appendix A: Classification of Asthma Severity), or currently has uncontrolled asthma
             of any classification. NOTE: subjects who currently have controlled intermittent
             asthma or controlled mild persistent asthma are allowed in the study.

         10. Subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis
             B surface antigen, or hepatitis C antibody (unless treated curatively).

         11. Subject has any concurrent medical condition or disease (e.g, active systemic
             infection) that is likely to interfere with study procedures or results, or that in
             the opinion of the investigator would constitute a hazard for participating in this
             study.

         12. Subject has any of the following laboratory test results at cycle 1 day 1 pre-dosing:
             1) Alanine aminotransferase level (ALT) >/= 2.5 x the upper limit of normal (ULN); 2)
             Aspartate Aminotransferase (AST) >/= 2.5 x the ULN; 3) Total bilirubin level >/= 1.5 x
             ULN, (except for Gilbert Syndrome: direct bilirubin >/= 1.5 x ULN); 4) Creatinine > 2
             x ULN.

         13. Subject has clinically significant cardiac disease, including: 1) myocardial
             infarction within 1 year before study enrollment, or an unstable or uncontrolled
             disease/condition related to or affecting cardiac function (e.g., unstable angina,
             congestive heart failure, New York Heart Association Class III-IV); 2)uncontrolled
             cardiac arrhythmia or clinically significant ECG abnormalities; 3) screening 12-lead
             ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470
             msec.

         14. Subject has known allergies, hypersensitivity, or intolerance to boron or mannitol,
             corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer
             to respective package inserts or Investigator's Brochure), or known sensitivity to
             mammalian-derived products.

         15. Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant
             while enrolled in this study or within 4 months after the last dose of any component
             of the treatment regimen. Or, subject is a man who plans to father a child while
             enrolled in this study or within 4 months after the last dose of any component of the
             treatment regimen.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) in Participants with Relapsed/Refractory B-Cell or T-Cell Precursor Acute Lymphoblastic Leukemia (ALL)
Time Frame:12 weeks
Safety Issue:
Description:Overall response (OR) defined as achievement of complete remission (CR), CR with only Partial Hematological Recovery (CRp), Complete Response without Hematological Recovery (CRi).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms stated as primary lymphoid haematopoietic
  • B-Cell Precursor Acute Lymphoblastic Leukemia
  • T-Cell Precursor Acute Lymphoblastic Leukemia
  • ALL
  • Daratumumab

Last Updated

September 7, 2017