Selinexor Plus High-Dose Melphalan (HDM) Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Phase 1/2 Investigator Sponsored Study of Selinexor in Combination With High-Dose Melphalan Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
1 other identifier
interventional
22
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 multiple-myeloma
Started Jul 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2016
CompletedFirst Posted
Study publicly available on registry
May 23, 2016
CompletedStudy Start
First participant enrolled
July 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 20, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 23, 2021
CompletedResults Posted
Study results publicly available
May 3, 2022
CompletedNovember 4, 2022
November 1, 2022
3.6 years
May 20, 2016
February 18, 2022
November 2, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Other Outcomes (3)
Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)
at 24 months
Overall Survival (OS)
at 24 months
Rate of Minimal Residual Disease (MRD)
3 months post HCT
Study Arms (1)
Selinexor Plus HDM HCT
EXPERIMENTALThe 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.
Interventions
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 100 mg/m\^2 IV over 30-45 minutes.
Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).
Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Fosaprepitant at 150 mg IV on days -3 and -2.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Related Publications (1)
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.
PMID: 33023948DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Taiga Nishihori, MD
- Organization
- Moffitt Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Taiga Nishihori, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2016
First Posted
May 23, 2016
Study Start
July 20, 2017
Primary Completion
February 20, 2021
Study Completion
February 23, 2021
Last Updated
November 4, 2022
Results First Posted
May 3, 2022
Record last verified: 2022-11