Selinexor, Ixazomib Citrate, and Low Dose Dexamethasone in Treating Patients with Relapsed or Refractory Multiple Myeloma

Status: Active

Description

This phase I trial studies the side effects and best dose of selinexor when given together with ixazomib citrate and low dose dexamethasone in treating patients with multiple myeloma that has come back or has not responded to treatment. Selinexor and ixazomib citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selinexor, ixazomib citrate, and dexamethasone may work better in treating patients with multiple myeloma.

Eligibility 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (within 14 days prior to registration)
  • Neutrophils >= 1.0 x 10^9/L (growth factor support is not allowed), (within 14 days prior to registration)
  • Platelet count >= 75 x 10^9/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, (within 14 days prior to registration)
  • Adequate hepatic and renal function laboratory values: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x the upper limit of normal (ULN) (within 14 days prior to registration)
  • Adequate hepatic and renal function laboratory values within 14 days prior to registration: Total bilirubin =< 1.5 mg/dL except for patients with a history of elevated total bilirubin, such as in Gilbert's
  • Adequate hepatic and renal function laboratory values within 14 days prior to registration: Calculated (Cockcroft and Gault formula) or measured creatinine clearance >= 30 mL/min
  • Left ventricular ejection fraction (LVEF) >= 40% within 28 days prior to registration, evaluated by 2-dimensional (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 (3-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 patient 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 gastrointestinal (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 cancer antigen (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 selective inhibitors of nuclear export (SINE) compound
  • Patients unwilling to comply with the protocol

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368
Rockville Centre
Memorial Sloan Kettering Rockville Centre
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Nikoletta Lendvai
Phone: 212-639-3368

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of selinexor and ixazomib citrate (ixazomib) when used in combination with low dose dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of selinexor and ixazomib citrate (ixazomib) when used in combination with low dose dexamethasone.

II. To describe the disease response of selinexor and ixazomib with low dose dexamethasone for MM patients treated at the MTD.

III. To bank a bone marrow and peripheral blood sample for future correlative studies.

TERTIARY OBJECTIVES:

I. To explore potential predictors of treatment response using the myeloma gene panel developed at Memorial Sloan-Kettering Cancer Center (MSKCC).

II. To explore potential pathways of resistance by comparing pre-treatment samples and samples at the time of either progression of disease or ongoing response using the myeloma gene panel.

III. To assess the impact on quality of life (QOL) of patients by utilizing the MD Anderson Symptom Inventory Multiple Myeloma Module (MDASI-MM).

OUTLINE: This is a dose escalation study of selinexor. Patients are assigned to 1 of 2 groups.

GROUP A: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15, dexamethasone PO on days 1, 3, 8, 10, 15, and 17, and selinexor PO on days 1, 3, 8, 10, 15, and 17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP B: Patients receive ixazomib citrate PO on days 1, 8, and 15, dexamethasone PO on days 1, 8, 15, and 22, and selinexor PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Nikoletta Lendvai

Trial IDs

Primary ID 15-310
Secondary IDs NCI-2016-01538
Clinicaltrials.gov ID NCT02831686