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

November 2, 2022 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • KPT-330
Drug: Melphalan
Melphalan 100 mg/m^2 IV over 30-45 minutes.
Other Names:
  • Alkeran
Drug: Dexamethasone
Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).
Other Names:
  • Decadron
Procedure: Autologous Hematopoietic Cell Transplantation (HCT)
Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Drug: Fosaprepitant
Fosaprepitant at 150 mg IV on days -3 and -2.
Other Names:
  • antiemetic agent
  • Standare of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Recommended Phase II Dose (RPh2D)
Time Frame: Up to 3 months
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)
Time Frame: 3 months post HCT

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)
Time Frame: at 24 months
Progression Free Survival defined as the time from start of treatment to the time of progression or death.
at 24 months
Overall Survival (OS)
Time Frame: at 24 months
Rate of participants' survival at time of evaluation.
at 24 months
Rate of Minimal Residual Disease (MRD)
Time Frame: 3 months post HCT
Rate of participants who did not have Minimal Residual Disease (MRD) as assessed by flow cytometry.
3 months post HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Karyopharm Therapeutics Inc

Investigators

  • Principal Investigator: Taiga Nishihori, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2017

Primary Completion (Actual)

February 20, 2021

Study Completion (Actual)

February 23, 2021

Study Registration Dates

First Submitted

May 20, 2016

First Submitted That Met QC Criteria

May 20, 2016

First Posted (Estimate)

May 23, 2016

Study Record Updates

Last Update Posted (Actual)

November 4, 2022

Last Update Submitted That Met QC Criteria

November 2, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-18630

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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