Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: To test whether the NFKB2 rearrangement can guide the selection of treatment (ixazomib [ixazomib citrate] plus dexamethasone [Id] or ixazomib plus lenalidomide and dexamethasone [IRd]) by conducting the following comparisons: I. To compare the response rate at 4 cycles between pa...

PRIMARY OBJECTIVES: To test whether the NFKB2 rearrangement can guide the selection of treatment (ixazomib [ixazomib citrate] plus dexamethasone [Id] or ixazomib plus lenalidomide and dexamethasone [IRd]) by conducting the following comparisons: I. To compare the response rate at 4 cycles between patients treated with Id and patients treated with IRd and confirm the lack of significant difference in overall response. II. To compare the response rate at 4 cycles between non-rearranged and rearranged NFKB2 treated with Id and confirm that NFKB2 rearrangement is associated with reduce response rate. III. To compare the responses rate at 4 cycles of patients with rearranged NFKB2 treated with Id or IRd and confirm that adding lenalidomide increases the response rate in this population. SECONDARY OBJECTIVES: I. To determine time to treatment failure (TTF). II. To determine the frequency and severity of adverse events (AE) in IRd treated cohort. III. To identify novel transcribed mutations associated with Id and IRd resistance in patients with multiple myeloma (MM). IV. To determine the prevalence of NFKB2 rearrangement in relapsed/refractory MM patients screened in the study. V. To determine the prevalence of NFKB2 rearrangement according to the type of previous therapies received in all patients screened in the study. VI. To determine the toxicity profile of the study drugs according to the presence of NFKB2 rearrangement. VII. Delineate transcribed mutations associated with relapse or refractoriness to Id or IRd treatment by ribonucleic acid (RNA)-sequencing. OUTLINE: ARM A (UNMUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib orally (PO) on days 1, 8, and 15 and dexamethasone PO on days 1, 8, 15, and 22. Patients with mutated NFKB2 rearrangement are randomized in to 1 of 2 treatment arms. ARM B (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A. ARM C (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A and lenalidomide PO daily on days 1-21. In all arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may proceed to autologous stem cell transplant after 4 cycles of treatment. After completion of study, patients are followed up monthly.

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