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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02780609
• Other study ID #: MCC-18630
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 20, 2017
• Est. completion date: February 23, 2021

Study information

• Verified date: November 2022
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 23, 2021
• Est. primary completion date: February 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.
• Melphalan
Melphalan 100 mg/m^2 IV over 30-45 minutes.
• Dexamethasone
Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).

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.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Karyopharm Therapeutics Inc

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Moffitt Cancer Center Clinical Trials website