Selinexor Combination Therapy

PRIMARY OBJECTIVE:

I. To evaluate the minimal residual disease (MRD) negativity rate, at 10^-5 level of sensitivity by flow cytometry in bone marrow, with the addition of selinexor to daratumumab, carfilzomib and dexamethasone (SKDd) in patients with high-risk, relapsed or relapsed/refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (partial response [PR] or better) of patients receiving SDKd combination for high risk, relapsed or relapsed/refractory multiple myeloma (MM) and assess depth of response (very good partial response [VGPR], complete response [CR], stringent complete response [sCR]).

II. To evaluate the time to response and duration of response in patients receiving SDKd combination for MM.

III. To evaluate the progression free survival and overall survival in patient receiving SDKd.

IV. To evaluate the MRD negativity rates to the level of sensitivity 10^-6 by flow cytometry in bone marrow.

V. To evaluate the safety profile of the SDKd combination.

CORRELATIVE RESEARCH OBJECTIVES:

I. To explore the impact of baseline immunomodulatory derivative (IMiD)-14 scores gene expression profile (GEP) on progression free survival.

II. Quality of life assessment utilizing Quality of Life Questionnaire (QLQ)-Core (C) 30 and QLQ-Multiple Myeloma (MY) 20 (Cocks et al., 2007; Wisloff et al., 1996).

OUTLINE:

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15 and daratumumab IV as a split dose on cycle 1 days 1 and 2 then on days 8, 15, and 22 of cycle 1, then on days 1, 8, 15, and 22 of cycle 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone orally (PO) on days 1, 8 15, and 22, and selinexor PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients without disease progression/clinical relapse or have initiated subsequent anti-cancer therapy, are followed up every 3 months until progression/clinical relapse or initiation of subsequent anti-cancer therapy, and then every 6 months for up to 5 years. Patients with disease progression/clinical relapse or have initiated subsequent anti-cancer therapy are followed up every 6 months for up to 5 years.