NCT04756401

Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma

Open Label, Phase 2, Single-Arm Study of Selinexor, Daratumumab, Carfilzomib and Dexamethasone for High-Risk, Relapsed and Relapsed/Refractory Multiple Myeloma Patients Who Have Received 1 - 3 Prior Lines of Therapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: Academic and Community Cancer Research United · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the effect of selinexor when combined with carfilzomib, daratumumab, and dexamethasone in treating patients with high-risk multiple myeloma that has come back (recurrent) or has not responded to treatment (refractory) and who have received 1-3 prior lines of therapy. Selinexor may stop the growth of cancer cells by blocking a protein called CRM1 that is needed for cell growth. Carfilzomib is a type of drug called a proteasome inhibitor. A proteasome is a protein found within cells that has the important role of identifying and marking damaged proteins that are needed to be destroyed by the cell for survival. The inhibition of the proteasome allows for damaged protein to accumulate within cells. This accumulation of damaged protein causes the cell to die. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving selinexor in combination with carfilzomib, daratumumab, and dexamethasone may work better than carfilzomib, daratumumab, and dexamethasone alone in treating patients with multiple myeloma.

Detailed description

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.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	Carfilzomib	Given IV
BIOLOGICAL	Daratumumab	Given IV
DRUG	Dexamethasone	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies
DRUG	Selinexor	Given PO

Timeline

• Start date: 2022-12-08
• Primary completion: 2024-09-30
• Completion: 2027-12-30
• First posted: 2021-02-16
• Last updated: 2024-09-26

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study