Selinexor, High-Dose Melphalan, and Dexamethasone before Stem Cell Transplant in Treating Patients with Multiple Myeloma

This phase I / II trial studies the side effects and best dose of selinexor and how well it works when given together with high-dose melphalan and dexamethasone before stem cell transplant in treating patients with multiple myeloma. Selinexor may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy, such as melphalan and dexamethasone, before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient’s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving selinexor, high-dose melphalan, and dexamethasone before stem cell transplant may work better in treating patients with multiple myeloma.

Inclusion Criteria

• Patients with histologically confirmed multiple myeloma
• Achieving partial response (PR) or very good partial response (VGPR) with systemic chemotherapy
• Received less than 4 lines of anti-myeloma therapy
• Karnofsky performance status of >= 70%
• Adjusted diffusion capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) >= 50% of predicted value (corrected for hemoglobin)
• Left ventricular ejection fraction (LVEF) >= 45%
• Total bilirubin =< 2 mg/dL; serum transaminases less than two times the institutional upper limit of normal (< 2 x upper limit of normal [ULN])
• Creatinine clearance >= 40 mL/min, estimated or calculated
• Signed informed consent form in accordance with institutional policies prior to the initiation of high-dose therapy

Exclusion Criteria

• Non-secretory multiple myeloma
• Patients who achieved complete response (CR) prior to autologous HCT
• Central nervous system (CNS) involvement
• Patients with uncontrolled bacterial, viral or fungal infections
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Patients with prior malignancies within the last 5 years except resected basal cell carcinoma or treated cervical carcinoma in situ
• Female patients who are pregnant (positive beta-human chorionic gonadotropin [B-HCG]) or breastfeeding
• Patients who have received other investigational drugs within 14 days prior to screening
• Prior autologous or allogeneic HCT
• Prior organ transplant or autoimmune disease requiring immunosuppressive therapy

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RPh2D)/maximum tolerated dose (MTD) of conditioning regimen of selinexor plus high-dose melphalan for autologous hematopoietic cell transplantation (HCT). (Phase I)

II. To assess complete response (CR) conversion rate at 3 months post autologous HCT. (Phase II)

SECONDARY OBJECTIVES:

I. To estimate overall response rate (ORR) at 3 months post autologous HCT.

II. To estimate progression-free survival (PFS) at 2 years.

III. To estimate overall survival (OS) at 2 years.

IV. To evaluate the cumulative incidence of engraftment post autologous HCT.

V. To assess minimal residual disease (MRD) with positron emission tomography (PET) scan, bone marrow flow cytometry and/or immunoglobulin gene sequencing at 3 months after autologous HCT (exploratory endpoint).

OUTLINE: This is a phase I, dose-escalation study of selinexor, followed by a phase II study.

Patients receive dexamethasone orally (PO) or intravenously (IV) once daily (QD) on days -3 to -1. Patients also receive selinexor PO QD on days -3 and -2, melphalan IV over 30-45 minutes on days -3 and -2, and fosaprepitant IV on days -3 and -2. Patients then undergo autologous HCT on day 0.

After completion of study treatment, patients are followed up for 90 days and periodically thereafter.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Moffitt Cancer Center

Principal Investigator
Taiga Nishihori

• Primary ID MCC-18630
• Secondary IDs NCI-2017-01190
• Clinicaltrials.gov ID NCT02780609