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

NCT ID: NCT02780609

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-20
• Study Completion Date: 2021-02-23

Brief Summary

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor Plus HDM HCT

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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.

Melphalan

Intervention Type: DRUG

Melphalan 100 mg/m\^2 IV over 30-45 minutes.

Dexamethasone

Intervention Type: DRUG

Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).

Autologous Hematopoietic Cell Transplantation (HCT)

Intervention Type: PROCEDURE

Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.

Fosaprepitant

Intervention Type: DRUG

Fosaprepitant at 150 mg IV on days -3 and -2.

Interventions

Selinexor

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.

Intervention Type: DRUG

Melphalan

Melphalan 100 mg/m\^2 IV over 30-45 minutes.

Intervention Type: DRUG

Dexamethasone

Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).

Intervention Type: DRUG

Autologous Hematopoietic Cell Transplantation (HCT)

Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.

Intervention Type: PROCEDURE

Fosaprepitant

Fosaprepitant at 150 mg IV on days -3 and -2.

Intervention Type: DRUG

Other Intervention Names

KPT-330; Alkeran; Decadron; antiemetic agent; Standare of Care

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Taiga Nishihori, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

Turner JG, Cui Y, Bauer AA, Dawson JL, Gomez JA, Kim J, Cubitt CL, Nishihori T, Dalton WS, Sullivan DM. Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma. Cancer Res. 2020 Dec 1;80(23):5344-5354. doi: 10.1158/0008-5472.CAN-19-0677. Epub 2020 Oct 6.

Reference Type: DERIVED

PMID: 33023948 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MCC-18630

Identifier Type: -

Identifier Source: org_study_id