ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02780609
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02780609
Recruitment Status : Recruiting
First Posted : May 23, 2016
Last Update Posted : December 4, 2018
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Selinexor Drug: Melphalan Drug: Dexamethasone Procedure: Autologous Hematopoietic Cell Transplantation (HCT) Drug: Fosaprepitant Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Investigator Sponsored Study of Selinexor in Combination With High-Dose Melphalan Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : August 31, 2020


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 Name: KPT-330

Drug: Melphalan
Melphalan 100 mg/m^2 IV over 30-45 minutes.
Other Name: Alkeran

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




Primary Outcome Measures :
  1. 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).

  2. Phase II: 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.



Other Outcome Measures:
  1. Progression Free Survival (PFS) [ Time Frame: 3 months post HCT ]
    Progressive Disease (PD) as outlined by International Myeloma Working Group (IMWG) uniform response criteria by response subcategory for multiple myeloma.

  2. Overall Survival (OS) [ Time Frame: 3 months post HCT ]
    Rate of participants' survival at time of evaluation.

  3. Rate of Minimal Residual Disease (MRD) [ Time Frame: 3 months post HCT ]
    To assess minimal residual disease (MRD) with PET scan, bone marrow flow cytometry and/or immunoglobulin gene sequencing at 3 months after autologous HCT (exploratory endpoint).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02780609


Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Caitlyn Ward    813-745-8986    caitlyn.ward@moffitt.org   
Contact: Taiga Nishihori, M.D.    813-745-8156    taiga.nishihori@moffitt.org   
Principal Investigator: Taiga Nishihori, M.D.         
Principal Investigator: Daniel Sullivan, M.D.         
Sub-Investigator: Melissa Alsina, M.D.         
Sub-Investigator: Rachid Baz, M.D.         
Sub-Investigator: Jose L. Ochoa-Bayona, M.D.         
Sub-Investigator: Kenneth Shain, M.D., Ph.D.         
Sub-Investigator: Joel Turner, Ph.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Taiga Nishihori, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02780609     History of Changes
Other Study ID Numbers: MCC-18630
First Posted: May 23, 2016    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
autologous hematopoietic cell transplantation (HCT)
high-dose melphalan
selinexor

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Antiemetics
Fosaprepitant
Aprepitant
Melphalan
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal