Selinexor, Pomalidomide, and Dexamethasone With or Without Carfilzomib for the Treatment of Patients With Relapsed Refractory Multiple Myeloma, The SCOPE Trial

Refractory Multiple Myeloma Clinical Trial

Official title: Phase 1/2 Trial of Selinexor in Combination With Pomalidomide and Dexamethasone ± Carfilzomib for Patients With Proteasome-Inhibitor and Immunomodulatory Drug Refractory Multiple Myeloma (SCOPE)

Status Recruiting

Clinical Trial Summary

This phase I/II trial identifies the best dose and side effects of selinexor, and how well it works when given in combination with pomalidomide and dexamethasone with or without carfilzomib in treating patients with multiple myeloma that has come back (relapsed) and does not respond to treatment with proteasome inhibitors and immunomodulatory drugs (refractory). Selinexor is an oral agent that blocks a protein called Exportin 1 (XPO1 or CRM1) that is abundant in a wide variety of cancers, including multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pomalidomide may stop the growth of blood vessels, stimulate the immune system, and kill cancer cells. Anti-inflammatory drugs, such as dexamethasone may lower the body's immune response and are used with other drugs in the treatment of some types of cancer. The addition of selinexor may allow better control of relapsed refractory multiple myeloma than is possible with pomalidomide and dexamethasone with or without carfilzomib.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of selinexor in combination with carfilzomib, pomalidomide and dexamethasone (SKPd) in patients with relapsed refractory multiple myeloma (RRMM). (Arm A) II. To determine the efficacy of fixed-dose selinexor in combination with low-dose pomalidomide and dexamethasone (SPd) in patients with RRMM as measured by the overall response rate (ORR) per the International Myeloma Working Group (IMWG) criteria. (Arm B)

SECONDARY OBJECTIVES:

I. To evaluate the preliminary efficacy of SKPd in relapsed/refractory multiple myeloma, as measured by the overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria and the duration of response (DOR). (Arm A) II. To evaluate clinical benefit rate (CBR), duration of response, progression-free survival, overall survival, and the safety profile of SPd. (Arm B)

EXPLORATORY OBJECTIVES:

I. To estimate clinical activity in different risk groups by cytogenetics. II. To assess minimal residual disease by flow cytometry in patients achieving complete response (CR) and compare the outcomes of patients who are serum mass-fix (mass spectrometry-based methodology available at Mayo Clinic) negative only versus those who have no evidence of disease by mass fix and flow-cytometry-based minimal residual disease (MRD).

III. To assess overall health-related quality of life, as measured by the global health domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Quality of Life Questionnaire-Multiple Myeloma 20 (QLQ-MY20).

IV. To evaluate patient reported outcomes using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Patient Reported Outcomes Version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]).

V. To stratify patients in arm A based on quadruple/penta-refractory status and to assess the impact of this stratification on patient outcomes.

VI. To stratify patients in arm B based on their dual-refractory status and to assess the impact of this stratification on patient outcomes.

OUTLINE: Patients with >= 3 prior lines of therapy are assigned to Arm A, while patients with 1-2 prior lines of therapy are assigned to Arm B. Arm A is a phase I dose-escalation study of selinexor and carfilzomib, with fixed-dose dexamethasone and pomalidomide followed by a dose-expansion study. Arm B is a phase II fixed-dose study of selinexor, dexamethasone, and pomalidomide.

ARM A: Patients receive selinexor orally (PO) and dexamethasone PO on days 1, 8 15, and 22, carfilzomib intravenously (IV) on days 1, 8, and 15, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo x-ray imaging during screening. Patients also undergo positron emission tomography/computed tomography (PET/CT) or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

ARM B: Patients receive selinexor PO and dexamethasone PO on days 1, 8, 15, and 22, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo x-ray imaging during screening. Patients also undergo PET/CT or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

After completion of study treatment, patients are followed up at 30 days, then every 3 months until progressive disease (PD) or subsequent treatment, then every 6 months until 3 years from registration. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

• NCT number: NCT04764942
• Study type: Interventional
• Source: Mayo Clinic
• Contact: Clinical Trials Referral Office
• Phone: 855-776-0015
• Email: mayocliniccancerstudies@mayo.edu
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 6, 2021
• Completion date: March 4, 2026