Clinical Trials /

Daratumumab in Treating Participants With Relapsed Multiple Myeloma After Stem Cell Transplant

NCT03622775

Description:

This phase II trial studies how well daratumumab works in treating participants with multiple myeloma that has come back after stem cell transplant. Immunotherapy with daratumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab in Treating Participants With Relapsed Multiple Myeloma After Stem Cell Transplant
  • Official Title: Daratumumab for Maintenance in Patients With Relapsed Multiple Myeloma After Salvage Autologous Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 2016-0681
  • SECONDARY ID: NCI-2018-01432
  • SECONDARY ID: 2016-0681
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03622775

Conditions

  • Recurrent Plasma Cell Myeloma

Interventions

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

Purpose

This phase II trial studies how well daratumumab works in treating participants with multiple myeloma that has come back after stem cell transplant. Immunotherapy with daratumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the complete remission rate (CRR) by the International Myeloma Working Group
      (IMWG) criteria within 9 months post salvage auto-transplant with daratumumab maintenance
      therapy starting approximately 3 months post salvage auto-transplant in patients with
      relapsed myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate progression-free survival (PFS).

      EXPLORATORY OBJECTIVES:

      I. To discover the impact of daratumumab on graft function and immune reconstitution.

      OUTLINE:

      Beginning 60-120 days after transplant, participants receive daratumumab intravenously (IV)
      over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6,
      then on day 1 of subsequent courses. Courses repeat every 28 days for 2 years in the absence
      of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 and 90 days, then
      every 4-12 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (daratumumab)ExperimentalBeginning 60-120 days after transplant, participants receive daratumumab IV over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6, then on day 1 of subsequent courses. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have had relapsed disease prior to transplant, or undergone previous
             autologous stem cell transplant (ASCT), followed by relapse and at least a partial
             response to salvage therapy

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 to 2

          -  Platelet count >= 50,000/mm^3 (within 5 days before the first dose of the study drug)

          -  Absolute neutrophil count >= 1000/ mm^3 (no growth factors within 5 days) (within 5
             days before the first dose of the study drug)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
             of normal (ULN) (within 5 days before the first dose of the study drug)

          -  Creatinine =< 2.5 mg/dL (within 5 days before the first dose of the study drug)

          -  Recovered (i.e., =< grade 2 toxicity) from the reversible effects of autologous stem
             cell transplant (within 5 days before the first dose of the study drug)

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care must be obtained, with the understanding that consent
             may be withdrawn by the subject at any time without any prejudice to future medical
             care

          -  Left ventricular ejection fraction >= 40%. No uncontrolled arrhythmias

        Exclusion Criteria:

          -  Major surgery within 14 days before the first dose of study drug

          -  Radiotherapy within 14 days before enrollment

          -  Non-secretory disease, plasma cell leukemia, or previous allogeneic transplant

          -  Already achieved CR at time of enrollment

          -  Known active central nervous system involvement

          -  Inability or unwillingness to comply with the drug administration requirements

          -  Female subject is pregnant or lactating

          -  Seropositive for human immunodeficiency virus (HIV)

          -  Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
             antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
             negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or
             antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time
             polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)
             deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded.
             EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs
             positivity as the only serologic marker) AND a known history of prior HBV vaccination,
             do not need to be tested for HBV DNA by PCR

          -  Seropositive for hepatitis C (except in the setting of a sustained virologic response
             [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)

          -  Known severe chronic obstructive pulmonary disease or asthma defined as forced
             expiratory volume in 1 second (FEV1) less than 60% of expected

          -  Infection requiring IV systemic antibiotic therapy within 7 days before cycle 1 day 1
             of therapy

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations

          -  Failure to have fully recovered (i.e., =< grade 2 toxicity) from the effects of prior
             chemotherapy regardless of the interval since last treatment

          -  Patient is refractory or resistant to daratumumab

          -  Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  If patient was unable to tolerate daratumumab in the past
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission rate (CRR) defined as achieving a negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow
Time Frame:At course 6 of therapy
Safety Issue:
Description:The student t-test/Wilcoxon rank test and analysis of variance (ANOVA)/Kruskal-Wallis test, or chi-squared test/Fisher's exact test will be used to test associations between the response and the prognostic factors. Complete remission will be estimated along with a 95% credible interval.

Details

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

Last Updated

May 7, 2019