Clinical Trials /

Daratumumab in Treating Transplant-Eligible Participants With Multiple Myeloma

NCT03477539

Description:

This phase II trial studies how well daratumumab works in treating transplant-eligible participants with multiple myeloma. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab in Treating Transplant-Eligible Participants With Multiple Myeloma
  • Official Title: Phase II Trial of Daratumumab for Transplant-Eligible Multiple Myeloma Patients

Clinical Trial IDs

  • ORG STUDY ID: MC1785
  • SECONDARY ID: NCI-2018-00332
  • SECONDARY ID: MC1785
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03477539

Conditions

  • Minimal Residual Disease
  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
DaratumumabAnti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Treatment (daratumumab, ASCT, lenalidomide)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (daratumumab, ASCT, lenalidomide)

Purpose

This phase II trial studies how well daratumumab works in treating transplant-eligible participants with multiple myeloma. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the percentage of patients achieving minimal residual disease (MRD)
      negativity by multiparameter flow cytometry (MPF) after autologous stem cell transplant (SCT)
      (at day 100) using pre-SCT daratumumab consolidation.

      SECONDARY OBJECTIVES:

      I. To determine percentage of patients achieving MRD negativity by MPF after 1 year of
      daratumumab+lenalidomide-based maintenance therapy.

      II. To determine progression-free survival (PFS) for peri-SCT treatment with daratumumab.

      III. To determine percentage of MRD negativity by MPF after pre-SCT consolidation with
      daratumumab.

      IV. To determine safety profile of peri-SCT daratumumab with lenalidomide. V. To determine
      the overall response rate (ORR) of patients receiving peri-SCT daratumumab for MM.

      VI. To determine the overall survival (OS) for patients receiving peri-SCT daratumumab for
      MM.

      EXPLORATORY OBJECTIVES:

      I. To correlate peripheral blood and bone marrow-based MRD testing using next generation
      sequencing (NGS). II. To correlate the MRD assessment by MPF with that by NGS at all the time
      points pre-specified for blood and bone marrow assessments.

      III. To profile the immune repertoire of MM patients while receiving maintenance treatment
      with daratumumab+lenalidomide.

      IV. Correlate antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent
      cell-mediated cytotoxicity (ADCC) with activity of daratumumab.

      V. To determine daratumumab-induced immune reconstitution of the host through eradication of
      immunosuppressive cellular elements.

      VI. To assess pharmacokinetics (PK) of every 3-month dosing of daratumumab.

      OUTLINE:

      CONSOLIDATION I: Participants receive daratumumab intravenously (IV) on days 1, 8, 15, and
      22. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression
      or unacceptable toxicity.

      CONSOLIDATION II: Beginning 8 weeks after completion of daratumumab course 2, participants
      undergo autologous stem cell transplant (ASCT).

      MAINTENANCE: Within 14 days after completion of day 100 visit post-SCT, participants receive
      daratumumab IV on day 1 and lenalidomide orally (PO) daily on days 1-21. Treatment repeats
      every 28 days for up to 12 courses in the absence of disease progression or unacceptable
      toxicity. Participants who are still maintaining response continue to receive daratumumab IV
      every 3 months in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 days and every 3-6
      months for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (daratumumab, ASCT, lenalidomide)ExperimentalCONSOLIDATION I: Participants receive IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION II: Beginning 8 weeks after completion of daratumumab course 2, participants undergo ASCT. MAINTENANCE: Within 14 days after completion of day 100 visit post-SCT, participants receive daratumumab IV on day 1 and lenalidomide PO daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Participants who are still maintaining response continue to receive daratumumab IV every 3 months in the absence of disease progression or unacceptable toxicity.
  • Daratumumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of multiple myeloma who are transplant eligible and
             have received any prior induction therapy (with or without maintenance)

          -  Measurable MRD in bone marrow within 28 days prior to registration (MPF method)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 at
             registration

          -  Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support,
             obtained =< 14 days prior to registration

          -  Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50%
             or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50%,
             obtained =< 14 days prior to registration

          -  Calculated or measured creatinine clearance >= 30 ml/min, obtained =< 14 days prior to
             registration

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert?s syndrome,
             in which case the direct bilirubin must be =< 1.5 X ULN, obtained =< 14 days prior to
             registration

          -  Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and
             alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =< 3 x ULN,
             obtained =< 14 days prior to registration

          -  Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 X ULN, obtained =<
             14 days prior to registration

          -  Negative urine or serum pregnancy test for women of childbearing potential

               -  NOTE: females of reproductive potential must adhere to the scheduled pregnancy
                  testing as required in the Revlimid REMS program

          -  Provide informed written consent

          -  Willing to provide bone marrow aspirate and core, and blood samples for correlative
             research purposes

          -  Measurable disease of multiple myeloma at the time of baseline values for disease
             assessment as defined by at least one of the following:

               -  Serum monoclonal protein >= 1.0 g/dL

               -  >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

               -  Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio ? Bone marrow plasma cells
                  >= 30%

        Exclusion Criteria:

          -  Any previous ASCT for multiple myeloma (MM)

          -  Any prior therapy with daratumumab

          -  Non-secretory MM or known amyloid light-chain (AL) amyloidosis

          -  Clinically significant active infection requiring intravenous antibiotics (=< 14 days
             prior to registration)

          -  >= grade 3 neuropathy and/or polyneuropathy, organomegaly, endocrinopathy, monoclonal
             protein, skin changes (POEMS syndrome)

          -  Other prior malignancy

               -  Exceptions:

                    -  Adequately treated basal cell or squamous cell skin cancer

                    -  Any in situ cancer

                    -  Adequately treated stage I or II cancer from which the patient is currently
                       in complete remission, or

                    -  Any other cancer from which the patient has been disease free for at least 3
                       years

          -  Concurrent therapy considered investigational

               -  NOTE: patients must not be planning to receive any radiation therapy (except
                  localized radiation for palliative care that must be completed prior to starting
                  cycle 1, day 1)

          -  Pregnant women

          -  Nursing women (lactating females are eligible provided that they agree not to breast
             feed while taking lenalidomide)

          -  Men or women of childbearing potential who are unwilling to employ adequate
             contraception

          -  Major surgery =< 4 weeks prior to registration

          -  History of stroke/intracranial hemorrhage =< 6 months prior to registration

          -  Clinically significant cardiac illness including New York Heart Association (NYHA)
             class III or class IV heart failure, unstable angina pectoris, myocardial infarction
             within the past 6 months, or >= grade 3 cardiac arrhythmias noted =< 14 days prior to
             registration

          -  Known human immunodeficiency virus positive (HIV+) patients

          -  Known hepatitis B or hepatitis C infection

          -  Exhibiting clinical signs of meningeal involvement of multiple myeloma

          -  Known severe chronic obstructive pulmonary disease or asthma defined as forced
             expiratory volume (FEV1) in 1 second less than < 60% of expected
      
Maximum Eligible Age:64 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of minimal residual disease (MRD) negative response after autologous stem cell transplantation (ASCT)
Time Frame:At day 100 post ASCT
Safety Issue:
Description:MRD negative response after ASCT is defined as achievement of MRD negative status in the bone marrow by flow cytometry (multiparameter flow cytometry [MPF]) at the day 100 post ASCT visit.

Secondary Outcome Measures

Measure:The rate of MRD negative response after pre-stem cell transplant (SCT) consolidation with daratumumab
Time Frame:Up to 3 years
Safety Issue:
Description:This will be estimated by the number of patients who achieve MRD negative status by flow cytometry (MPF) in the bone marrow after pre-SCT consolidation with daratumumab divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of MRD negative response after pre-SCT consolidation with daratumumab will be calculated.
Measure:Rate of MRD negative response after 1 year (12 courses) of daratumumab and lenalidomide maintenance
Time Frame:At 1 year (12 courses) of daratumumab and lenalidomide maintenance
Safety Issue:
Description:This will be estimated by the number of patients who achieve MRD negative status by flow cytometry (MPF) in the bone marrow after 1 year of maintenance therapy divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of MRD negative response after 1 year of maintenance will be calculated.
Measure:Progression-free survival
Time Frame:From registration up to 3 years
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the Kaplan-Meier method.
Measure:Survival time
Time Frame:From registration up to 3 years
Safety Issue:
Description:The distribution of survival time will be estimated using the Kaplan-Meier method.
Measure:Overall response rate
Time Frame:At day 100 post ASCT
Safety Issue:
Description:This will be estimated by the number of patients with an objective status of stringent complete responses, complete response, very good partial response, or partial response at the day 100 post ASCT assessment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate at day 100 post ASCT will be calculated.
Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

May 1, 2019