Clinical trial NCT02780609: Selinexor Plus High-Dose Melphalan (HDM) Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Official title: Phase 1/2 Investigator Sponsored Study of Selinexor in Combination With High-Dose Melphalan Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: autologous hematopoietic cell transplantation (HCT)
high-dose melphalan
selinexor
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Karyopharm Therapeutics Inc
First posted: 2016-05-23
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase I: Recommended Phase II Dose (RPh2D)
timeFrame: Up to 3 months
measure: Complete Response (CR)
timeFrame: 3 months post HCT
Secondary outcomes:
Other outcomes:
measure: Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)
timeFrame: at 24 months
measure: Overall Survival (OS)
timeFrame: at 24 months
measure: Rate of Minimal Residual Disease (MRD)
timeFrame: 3 months post HCT
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Taiga Nishihori, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.