Clinical Trials /

Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT03067571

Description:

This phase II trial studies how well daratumumab works in treating patients with acute myeloid leukemia that has come back or does not respond to treatment or high-risk myelodysplastic syndrome. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
  • Official Title: An Open-Label, Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: 2016-0889
  • SECONDARY ID: NCI-2018-01222
  • SECONDARY ID: 2016-0889
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03067571

Conditions

  • High Risk Myelodysplastic Syndrome
  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
DaratumumabAnti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Treatment (daratumumab)

Purpose

This phase II trial studies how well daratumumab works in treating patients with acute myeloid leukemia that has come back or does not respond to treatment or high-risk myelodysplastic syndrome. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess response rate as determined by the International Working Group recommendations.

      SECONDARY OBJECTIVES:

      I. To assess safety and tolerability. II. To assess time on treatment. III. To assess overall
      survival. IV. To assess progression free survival. V. To assess long-term response rate.

      EXPLORATORY OBJECTIVES:

      I. To explore biomarkers predictive of response or resistance to therapy including expression
      of CD38 at study entry and at relapse and response rate based on CD38 expression level.

      OUTLINE:

      Patients receive daratumumab intravenously (IV) over 3.25-6.5 hours on days 1, 8, 15 and 22
      of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles
      repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up monthly for 1 year, every 6
      months for 1 year, and then annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (daratumumab)ExperimentalPatients receive daratumumab IV over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Diagnosis of acute myeloid leukemia (AML) (other than acute promyelocytic leukemia
             [APL]) with refractory/relapsed disease; patients with relapsed/refractory high-risk
             ([intermediate-2 or higher by International Prognostic Scoring System [IPSS] and/or >=
             10% blasts]). Myelodysplastic syndrome (MDS) will also be eligible. (Treatment
             approach for relapsed/refractory AML is very similar to that of high risk MDS)

          -  All non-hematological toxicity of previous cancer therapy should have resolved to =<
             grade 1 (except alopecia or other toxicities not involving major organs)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

          -  Serum creatinine =< 2 mg/dL and estimated glomerular filtration rate or creatinine
             clearance >= 20 ml/min

          -  Total bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper
             limit of normal (ULN)

          -  Women of childbearing potential must be practicing a highly effective method of birth
             control consistent with local regulations regarding the use of birth control methods
             for subjects participating in clinical studies: eg, established use of oral, injected
             or implanted hormonal methods of contraception; placement of an intrauterine device or
             intrauterine system; barrier methods: condom with spermicidal
             foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps)
             with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
             vasectomized partner should be the sole partner for that subject); true abstinence
             (when this is in line with the preferred and usual lifestyle of the subject) during
             and after the study (3 months after the last dose of daratumumab for women)

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control eg, either condom with
             spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
             must also not donate sperm during the study and for 3 months after receiving the last
             dose of study drug

          -  AML relapse > 6 months since autologous or allogeneic stem cell transplantation,
             provided there is no active graft-versus-host disease (GVHD) > grade 1; no treatment
             with high dose steroids for GVHD (up to 20 mg prednisolone or equivalent); no
             treatment with immunosuppressive drugs with the exception of low dose cyclosporine and
             tacrolimus (blood levels of 0.5-0.6 ug/mL)

        Exclusion Criteria:

          -  Pregnant or breast feeding females

          -  Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (exception
             hydroxyurea). Use of hydroxyurea to control proliferative disease will be allowed
             prior to starting therapy on study and for 7 days during cycle 1-3 (maximum daily dose
             of 7 gm)

          -  Subject has received daratumumab or other anti-CD38 therapies previously

          -  Subject has received a cumulative dose of corticosteroids more than the equivalent of
             >= 140 mg of prednisone within the 2 week period before cycle 1, day 1

          -  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

          -  Subject has a history of another malignancy within 5 years before cycle 1, day 1
             (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ
             of the cervix, or malignancy that in the opinion of the investigator, with concurrence
             with the IND office and supporter's medical monitor, is considered cured with minimal
             risk of recurrence)

          -  Subject is known to be seropositive for human immunodeficiency virus (HIV) or
             hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or
             antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc,
             respectively]) or hepatitis C (anti-hepatitis C virus [HCV] antibody positive or
             HCV-ribonucleic acid [RNA] quantitation positive)

          -  Subject has clinically significant cardiac disease, including: myocardial infarction
             within 1 year before cycle 1, day 1, or unstable or uncontrolled disease/condition
             related to or affecting cardiac function (eg, unstable angina, congestive heart
             failure, New York Heart Association class III-IV); cardiac arrhythmia (Common
             Terminology Criteria for Adverse Events [CTCAE] version 4.03 grade 2 or higher) or
             clinically significant electrocardiogram (ECG) abnormalities; screening 12-lead ECG
             showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec

          -  Subject has known severe allergies, hypersensitivity, or intolerance to monoclonal
             antibodies or human proteins, or their excipients (refer to the latest version of the
             Investigator Brochure), or known sensitivity to mammalian-derived products

          -  Subject has any concurrent medical condition or disease (eg, active systemic
             infection, laboratory abnormalities) 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

          -  Exclude patients with known Kell antibodies
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate as determined by the International Working Group recommendations
Time Frame:Up to 3.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure:Time on treatment
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure:Long-term response rate
Time Frame:Up to 3.5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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