Clinical Trial 20413

• Overview

  Study Title:

  Phase III Study Of Daratumumab/Rhuph20 (Nsc- 810307) + Lenalidomide Or Lenalidomide As Post-Autologous Stem Cell Transplant Maintenance Therapy In Patients With Multiple Myeloma (MM) Using Minimal Residual Disease To Direct Therapy Duration (DRAMMATIC STUDY)

  Summary:

  Participants are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Participants are treated for up to 7 years from Step 2 reg and followed for up to 15 years.

  Objective:

  Primary Objective: To compare overall survival (OS) between the two treatment arms with lenalidomide as the comparator arm and lenalidomide + daratumumab/rHuPH20 as the experimental arm in post-autologous transplant multiple myeloma (MM) patients. Secondary Objectives of First Randomization: To compare the best overall response rate (ORR), including partial remission (PR), very good partial remission (VGPR), and complete remission (CR, sCR) in the subset of patients not in PR at randomization to lenalidomide versus lenalidomide + daratumumab/rHuPH20 in this patient population. To compare progression-free survival (PFS) between the study arms in this patient population. To evaluate MRD-negativity on the two treatment arms at randomization (Registration Step 2), and to compare MRD-negativity rate at 12, 24 (second randomization), 36, and 48 months after first randomization between lenalidomide and lenalidomide + daratumumab/rHuPH20 in this patient population. To compare toxicities and tolerability of long term therapy between the study arms. Objectives of Second Randomization: To compare overall survival (OS) between MRD negative patients randomized to continued lenalidomide vs. discontinued lenalidomide from the time of second randomization in this patient population. To compare overall survival (OS) between MRD negative patients randomized to continued lenalidomide + daratumumab/rHuPH20 vs. discontinued lenalidomide + daratumumab/rHuPH20 from time of second randomization in this patient population.

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  CC-5013 (Lenalidomide); Daratumumab/rHuPH20 (); Lenalidomide (Revlimid)

• Inclusion Criteria

  • Participants must have had a confirmed diagnosis of symptomatic multiple myeloma that required systemic induction therapy prior to autologous stem cell transplantation
  • Participants with disease measurable by serum light chain assay alone are eligible (defined as >/= 100 mg/L on involved light chain).
  • Participants must be registered to Step 1 prior to registration to Step 2. Registration to Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but after completion of induction therapy.
  • Participants must have initiated induction therapy within 18 months prior to registration Step 1 and have received at least two cycles of induction therapy.
  • Participants must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation).
  • Participants must be >/= 18 and > Participants must have history and physical exam within 28 days prior to registration.
  • Participants must have Zubrod Performance Status > Participants must have evidence of adequate renal function, as defined by (1) creatinine clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or (2) serum creatinine > Participants must have adequate hepatic function defined by the following within 42 days prior to registration: Total bilirubin > Participants must meet one of the following criteria: Be acceptable for transplant per institutional guidelines OR Have completed autologous stem cell transplant within 180 days prior to registration
  • Participants with HIV are eligible providing they are on effective antiretroviral therapy and have undetectable viral load at their most previous viral load test and within 6 months prior to registration.
  • Participants must be able to take and swallow oral medication whole. Participants may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug
  • For Participants who have not yet received transplant: Participants must be willing and able to return to the transplant center for their assigned treatment after randomization. Note that Participants need not have a direct relationship with the transplant center in order to register.
  • Patient-Reported Outcomes Criterion: Patients who can complete patient-reported outcomes instruments in English or Spanish must agree to complete the assessments described in Section 15.3 at the protocol-specified time pointes.

• Exclusion Criteria

  • Participants with smoldering myeloma are not eligible. Participants with purely non-secretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible. Participants must have measurable M protein in the serum (defined as >/= 0.5g/dL) or urine (defined as >/= 200 mg/24h). Participants with plasma cell leukemia are not eligible.
  • Participants must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
  • Participants must not have progressive disease at any time prior to registration.
  • Participants must not be refractory to either lenalidomide or daratumumab/rHuPH20.
  • Participants must not be intolerant to either lenalidomide or daratumumab/rHuPH20.
  • Participants must not have received any investigational agents within 14 days prior to registration.
  • Participants must not have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) > Participants must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
  • Participants must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy.
  • Participants must not have known allergy to any of the study drugs.
  • Participants with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible.
  • Participants must not have known central nervous system (CNS) involvement with multiple myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS plasmacytoma at time of enrollment
  • Participants must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). HCV testing is only required if clinically indicated or if the patient has a history of HCV.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical 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 three years.
  • Participants must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade >/= 2), intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>/= Grade 3), or known psychiatric illness that would limit study compliance.

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