Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma

Description

PRIMARY OBJECTIVES:

I. To compare overall survival in patients with high-risk smoldering multiple myeloma randomized to daratumumab-lenalidomide (revlimid)-dexamethasone or revlimid-dexamethasone.

SECONDARY OBJECTIVES:

I. To compare progression-free survival and response rates between arms. II. To evaluate safety and compare toxicity rates between arms. III. To monitor incidence of infusion-related reactions over the first cycle of daratumumab.

IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility.

EXPLORATORY OBJECTIVES:

I. To measure treatment exposure and adherence. II. To estimate treatment duration and time to progression.

PATIENT-REPORTED OUTCOMES OBJECTIVES:

I. To compare change in health-related quality of life (Functional Assessment of Cancer Therapy [FACT]- General [G]]) from baseline to end of study therapy between arms.

II. To compare change in FACT-G scores from treatment end to 6-months post-treatment end between arms.

III. To describe changes in FACT-G scores over study therapy and shortly after treatment discontinuation and evaluate correlation with survival.

IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally.

V. To derive an overall PRO-CTCAE score at each assessment time point. VI. To measure the likelihood of medication adherence (ASK-12) at 6 month intervals throughout treatment.

VII. To assess the association of overall PRO-CTCAE score with FACT-G score. VIII. To compare select PRO-CTCAE items and related provider-reported CTCAEs. IX. To evaluate association between treatment adherence and Adherence Starts with Knowledge 12 (ASK-12) score.

X. To assess correlation of treatment adherence and ASK-12 score with FACT-G score.

XI. To tabulate PRO compliance and completion rates.

LABORATORY OBJECTIVES:

I. To compare minimal residual disease negative rate after 12 cycles of study therapy between arms.

II. To compare minimal residual disease (MRD) positive to negative conversion rates from 12 cycles to end of treatment between arms.

III. To examine patterns of change in minimal residual disease levels during study therapy.

IV. To evaluate agreement and discordance between methods determining disease-free status.

V. To assess the prognostic value of minimal residual disease status at 12 cycles for overall and progression-free survival.

IMAGING OBJECTIVES:

I. To evaluate the association of baseline fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging with progression-free survival.

II. To assess the ability of baseline FDG-PET/CT to predict minimal residual disease status after 12 cycles of study therapy and at the end of study therapy.

III. To describe the results of subsequent FDG-PET/CT imaging studies in the subset of patients with baseline abnormal FDG-PET/CT, and to associate these results with progression-free survival (PFS).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of courses 7-24. Patients also receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 in courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study, patients will be followed up every 3, 6 or 12 months for up to 15 years from study entry.

Details