A Study to Test the Combination of Selinexor (KPT-330), Ixazomib, and Dexamethasone in Patients With Myeloma

NCT02831686 | Completed Phase 1

• 1 other identifier: 15-310
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of a combination of study drugs called selinexor (KPT-330) and ixazomib (MLN9708) with a low dose of dexamethasone. This study tests different doses of the study drug, selinexor to see which dose is safer in people. Depending on which group (dose level) you are in, the dose of selinexor will vary, but the ixazomib and dexamethasone doses will be the same among the groups.

Conditions

Multiple Myeloma; Relapsed and/or Refractory Multiple Myeloma

Keywords

Selinexor (KPT-330); Ixazomib; dexamethasone; 15-310

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  This study will follow a 3-by-3 dose escalation design.

  1 year

Study Arms (1)

Selinexor (KPT-330), Ixazomib, and Dexamethasone

EXPERIMENTAL

Patients with relapsed and/or refractory MM will be treated with ixazomib, selinexor, and dexamethasone, all of which will be administered orally.Ixazomib will be given on Days 1, 8, and 15 on a 28 day cycle. Selinexor will be given twice weekly for three weeks, then there will be 1 week off (Days 1,3, 8,10, 15, 17) This study will follow a 3-by-3 dose escalation design. Dexamethasone will be given on all days of Selinexor but will also be given on the week off from Selinexor (Days 1, 3, 8, 10,15, 17, 22, 24).

Drug: Selinexor; Drug: Ixazomib; Drug: Dexamethasone

Interventions

Selinexor DRUG

Also known as: (KPT-330)

Selinexor (KPT-330), Ixazomib, and Dexamethasone

Ixazomib DRUG

Selinexor (KPT-330), Ixazomib, and Dexamethasone

Dexamethasone DRUG

Selinexor (KPT-330), Ixazomib, and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MSKCC confirmed diagnosis of multiple myeloma that has relapsed or is resistant after therapy with at least one immunomodulatory drug (i.e. lenalidomide, thalidomide) and at least one proteasome inhibitor.
• Measurable multiple myeloma disease, defined as meeting at least 1 of the following criteria within 14 days prior to registration:
• A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 0.5 g/dL.
• Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
• Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC ratio is abnormal.
• Presence of extramedullary plasmacytomas.
• Patient must be ≥ 18 years of age at time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to registration.
• Adequate hematology laboratory values within 14 days prior to registration:
• Neutrophils ≥ 1.0 × 10\^9/L (growth factor support is not allowed).
• Platelet count ≥75x10\^9/L. Platelet support is permitted within 14 days although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours (3 days) prior to the blood sample to confirm protocol eligibility.
• Adequate hepatic and renal function laboratory values within 14 days prior to registration:
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 mg/dL except for patients with a history of elevated total bilirubin, such as in Gilbert's.
• Calculated (Cockcroft and Gault formula) or measured creatinine clearance ≥ 30mL/min.

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Failure to have fully recovered from the reversible effects of prior anti-cancer therapy.
• Major surgery within 14 days prior to the first dose of study drug.
• Radiotherapy within 14 days prior to the first dose of study drug. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the first dose of the study medications.
• Disease-related central nervous system involvement.
• The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris within 6 months, stroke within 6 months, myocardial infarction within 6 months, or uncontrolled cardiac arrhythmias, uncontrolled hypertension.
• Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Known GI disease or GI procedure that could interfere with the oral absorption of study medication including difficulty swallowing.
• Concurrent malignancy except for treated non-melanoma skin cancer, cervical carcinoma in situ and low-risk prostate CA being monitored without treatment.
• Patient has Grade 3 peripheral neuropathy or Grade 2 with pain on clinical examination during the screening period.
• Chemotherapy within 14 days of the start of this trial.
• Prior exposure to a SINE compound.
• Patients unwilling to comply with the protocol.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Karyopharm Therapeutics Inc: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (7)

Memoral Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; ixazomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Malin Hultcrantz, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2016
• First Posted: July 13, 2016
• Study Start: July 1, 2016
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: November 24, 2020

Record last verified: 2020-11

Locations

US (7)