ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Test the Combination of Selinexor (KPT-330), Ixazomib, and Dexamethasone in Patients With 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: NCT02831686
Recruitment Status : Recruiting
First Posted : July 13, 2016
Last Update Posted : May 25, 2018
Sponsor:
Collaborators:
Karyopharm Therapeutics Inc
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Relapsed and/or Refractory Multiple Myeloma Drug: Selinexor Drug: Ixazomib Drug: Dexamethasone Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Investigator-Initiated Phase I Study of Selinexor (KPT-330), Ixazomib, and Low Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date : July 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019


Arm Intervention/treatment
Experimental: Selinexor (KPT-330), Ixazomib, and Dexamethasone

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
Other Name: (KPT-330)

Drug: Ixazomib
Drug: Dexamethasone



Primary Outcome Measures :
  1. maximum tolerated dose (MTD) [ Time Frame: 1 year ]
    This study will follow a 3-by-3 dose escalation design.



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:

  • 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.
  • Left ventricular ejection fraction (LVEF) ≥ 40% within 28 days prior to registration, evaluated by 2-D transthoracic echocardiogram (ECHO) or, if ECHO is not available, by multi-gated acquisition (MUGA) scan.
  • Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)If patient is female and of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (β-HCG) test within 14 days prior to registration and consent to ongoing pregnancy testing during the course of the study.
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.

  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
  • Written informed consent in accordance with federal, local, and institutional guidelines. The patients must provide informed consent prior to the first screening procedure.

Exclusion Criteria:

  • 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.

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): NCT02831686


Contacts
Contact: Nikoletta Lendvai, MD, PhD 212-639-3368
Contact: Ola Landgren, MD, PhD 212-639-5126

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Nikoletta Lendvai, MD, PhD    212-639-3368      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Nikoletta Lendvai, MD    212-639-3368      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Nikoletta Lendvai, MD, PhD    212-639-3368      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Nikoletta Lendvai, MD, PhD    212-639-5126      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Nikoletta Lendvai, MD, PhD    212-639-3368      
Contact: Ola Landgren, MD, PhD    212-639-5126      
Principal Investigator: Nikoletta Lendvai, MD, PhD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Nikoletta Lendvai, MD, PhD    212-639-3368      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Karyopharm Therapeutics Inc
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Nikoletta Lendvai Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02831686     History of Changes
Other Study ID Numbers: 15-310
First Posted: July 13, 2016    Key Record Dates
Last Update Posted: May 25, 2018
Last Verified: May 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:
Selinexor (KPT-330)
Ixazomib
dexamethasone
15-310

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
Ixazomib
BB 1101
Glycine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents