Daratumumab, Ixazomib, and Dexamethasone with or without Bortezomib in Treating Patients with Newly Diagnosed Multiple Myeloma

Summary

Objectives

PRIMARY OBJECTIVE:
I. To determine the >= very good partial response (VGPR) rate after 8 cycles in subjects treated with daratumumab and hyaluronidase-fihj (daratumumab), ixazomib and dexamethasone (DId) versus (vs) daratumumab, bortezomib and dexamethasone (DVd) followed by DId among newly diagnosed myeloma patients (NDMM).

SECONDARY OBJECTIVES:
I. To estimate the proportion of subjects with successful stem cell mobilization after receiving 3 cycles of treatment in both arms (DId x 8 vs DVd x 3 then DId x 5).
II. To establish safety among patients receiving the combination of DId and DVd then DId.
III. To obtain anti-tumor activity (best response rates: overall response rate [ORR], VGPR, complete response [CR], stringent complete response [sCR] and minimal residual of disease [MRD] negativity) in patients treated with these combinations.
IV. Progression free survival (PFS), progression free survival 2 (PFS2), duration of response (DOR), time to progression (TTP), determine the time to next therapy (TTNT).
V. Overall survival (OS).
VI. Engraftment parameters among the autologous stem cell transplant (ASCT) group.
VII. Determine whether tumor response and PFS may change in subgroups with different prognosis according to current prognostic factors.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:
INDUCTION: Patients receive dexamethasone intravenously (IV) and orally (PO) on days 1, 8, 15, and 22, daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-8, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance.

MAINTENANCE: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab and hyaluronidase-fihj SC on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

ARM II:
INDUCTION CYCLES 1-3: Patients receive dexamethasone IV and PO on days 1, 8, and 15, daratumumab and hyaluronidase-fihj SC on days 1, 8, and 15, and bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity.

INDUCTION CYCLES 4-8: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab and hyaluronidase-fihj SC on days 1 and 15, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance.

MAINTENANCE: Patients receive dexamethasone IV on day 1, daratumumab and hyaluronidase-fihj SC on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.