Testing the Addition of a New Drug, Daratumumab/rHuPH20, to the Usual Treatment (Lenalidomide) as Post-stem Cell Transplant Treatment for Multiple Myeloma, DRAMMATIC Study

Summary

Objectives

PRIMARY OBJECTIVE:
I. 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:
I. To compare the best overall response rate (ORR), including partial remission (PR), very good partial remission (VGPR), and complete remission (CR, stringent [s]CR) in the subset of patients not in PR at randomization to lenalidomide versus lenalidomide + daratumumab/rHuPH20 in this patient population.
II. To compare progression-free survival (PFS) between the study arms in this patient population.
III. To evaluate MRD-negativity (<10*-6 by next-generation sequencing [NGS]) on the two treatment arms at randomization (Registration Step 2), and to compare MRD-negativity at 12, 24 (second randomization), 36, and 48 months after first randomization between lenalidomide and lenalidomide + daratumumab/rHuPH20 in this patient population.
IV. To compare toxicities and tolerability of long term therapy between the study arms.

OBJECTIVES OF SECOND RANDOMIZATION:
I. To compare overall survival (OS) between MRD (<10^-6 by NGS) negative patients randomized to continued lenalidomide versus (vs.) discontinued lenalidomide from the time of second randomization in this patient population.
II. To compare overall survival (OS) between MRD negative (<10^-6 by NGS) patients randomized to continued lenalidomide + daratumumab/rHuPH20 vs. discontinued lenalidomide + daratumumab/rHuPH20 from time of second randomization in this patient population.

ADDITIONAL OBJECTIVES:
I. To report the findings of the 24-month MRD analysis as early as 24 months after all patients have been accrued.
II. To compare patient-reported health-related quality of life at 24 months after first randomization (approximately 2 years post-transplant) and at 48 months after first randomization (4 years post-transplant and 2 years after second randomization) in patients with multiple myeloma randomized to Daratumumab/rHuPH20 (NSC- 810307) + Lenalidomide versus Lenalidomide post-autologous stem cell transplantation (ASCT) using the Patient-Reported Outcomes Measurement Information System (PROMIS) 29.
III. To compare select patient-reported outcomes using the Common Terminology Criteria for Adverse Events (PRO-CTCAE) by arm.
IV. Among patients with conclusive MRD results at 24 months after first randomization, to compare responses to the Intolerance of Uncertainty Scale Short Form (IUS) and the PROMIS-29 by MRD status.
V. To explore whether PROMIS-29 scores at baseline (Registration Step 2) and 24 months (both first and second randomizations) are associated with PFS, and whether the effect of randomized assignment on PFS differs according to baseline PROMIS-29 levels

OUTLINE: Patients are randomized to 1 of 2 arms after undergoing autologous stem cell transplantation.

ARM I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who achieve MRD negativity (< 10^-6 by NGS) are then randomized to continue lenalidomide treatment for 5 years or stop treatment. Patients who are MRD positive continue lenalidomide treatment for 5 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive lenalidomide PO QD on days 1-28. Patients also receive daratumumab/rHuPH20 subcutaneously (SC) over 3-5 minutes on days 1, 8, 15 and 22 of cycles 1-2, days 1 and 15 for cycles 3-6, and day 1 for subsequent cycles. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who achieve MRD negativity (< 10^-6 by NGS) are then randomized to continue lenalidomide and daratumumab/rHuPH20 treatment for 5 years or stop treatment. Patients who are MRD positive continue lenalidomide and daratumumab/rHuPH20 treatment for 5 years in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspirate and/or biopsy, bone scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan throughout the study.

After completion of study treatment, patients are followed up every 2 or 6 months for 7 years, and then annually for up to 15 years after Registration Step 2.