Selinexor Plus High-Dose Melphalan (HDM) Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Study Overview
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Brief Summary
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Phase I: The primary purpose of this study phase is to determine the best dose also referred to as the maximum tolerated dose (MTD) of Selinexor when used in combination with high-dose melphalan as a conditioning regimen for hematopoietic cell transplant. Phase II: The primary purpose of this study phase is to assess the complete response (CR) conversion rate.

Official Title
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Phase 1/2 Investigator Sponsored Study of Selinexor in Combination With High-Dose Melphalan Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Selinexor
* Drug: Melphalan
* Drug: Dexamethasone
* Procedure: Autologous Hematopoietic Cell Transplantation (HCT)
* Drug: Fosaprepitant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older 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% Adequate pulmonary, cardiac, hepatic and renal function as outlined in the protocol Signed informed consent form in accordance with institutional policies prior to the initiation of high-dose therapy Exclusion Criteria: Non-secretory multiple myeloma Have achieved complete response (CR) prior to autologous hematopoietic cell transplantation (HCT) Central nervous system (CNS) involvement 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. Prior malignancies within the last 5 years except resected basal cell carcinoma or treated cervical carcinoma in situ. Females who are pregnant or breastfeeding 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor Plus HDM HCT<br>The conditioning regimen begins 3 days prior to autologous transplant. Day 0 is the day of the autologous hematopoietic cell transplant. Melphalan will be given intravenously (IV) on Day -3 and Day -2; Dexamethasone will be given through via IV on Day -3, Day -2 and Day -1; fosaprepitant at 150 IV on days -3 and -2 will be given to patients an an antiemetic.Selinexor will be taken by mouth (PO) daily on the same day participants receive chemotherapy with melphalan. | Drug: Selinexor<br>* Selinexor will be given orally 2 to 3 hours prior to high dose-melphalan IV infusion. Phase I: Dose escalation beginning with 40 mg to determine the recommended Phase II dose (RPh2D). Phase II: Treatment at RPh2D.<br>* Other names: KPT-330;Drug: Melphalan<br>* Melphalan 100 mg/m^2 IV over 30-45 minutes.<br>* Other names: Alkeran;Drug: Dexamethasone<br>* Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).<br>* Other names: Decadron;Procedure: Autologous Hematopoietic Cell Transplantation (HCT)<br>* Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.<br>Drug: Fosaprepitant<br>* Fosaprepitant at 150 mg IV on days -3 and -2.<br>* Other names: Standare of Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Recommended Phase II Dose (RPh2D) | RPh2D/Maximum Tolerated Dose (MTD) of Selinexor when used in combination with high-dose melphalan as a conditioning regimen for hematopoietic cell transplant. MTD: the highest dose level at which 1 or less of 6 participants experience a dose limiting toxicity (DLT). | Up to 3 months | 
| Complete Response (CR) | Complete response (CR) conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. Complete Response conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. | 3 months post HCT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous hematopoietic cell transplantation (HCT), high-dose melphalan, selinexor