Treatment of Selinexor in Combination With Clarithromycin, Pomalidomide and Dexamethasone for Relapsed Refractory Multiple Myeloma Patients

Study Purpose

The purpose of this study is to determine the efficacy and safety of investigational combination therapy of Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd) for patients with relapsed/refractory multiple myeloma. The hypothesis is that the addition of Selinexor to Clarithromycin, Pomalidomide and Dexamethasone will increase the overall response rate of patients with relapsed/refractory multiple myeloma.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 74 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Written informed consent in accordance with federal, local, and institutional guidelines.
  • - Age ≥18 and <75 years at the time of informed consent.
  • - Confirmed diagnosis of multiple myeloma.
  • - Symptomatic multiple myeloma per IMWG guidelines.
  • - Measurable disease as defined by at least one of the following: a.
Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA, and/or b. Urinary M-protein excretion at least 200 mg/24 hours, and/or c. Serum FLC ≥ 100 mg/L, provided that FLC ratio is abnormal, and/or d. If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement (e.g., for IgA MM), then quantitative Ig levels by nephelometry or turbidimetry are acceptable.
  • - Relapsed and refractory multiple myeloma with documented evidence of PD after achieving at least SD for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM), and ≤ 25% response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM).
  • - Previously received one to four prior lines of therapy and be pomalidomide-naïve.

Exclusion Criteria:

  • - Documented active systemic light chain amyloidosis.
  • - Active plasma cell leukemia.
  • - Eastern Cooperative Oncology Group (ECOG) Performance Status greater than 2.
  • - Persistent non-hematological toxicity (except for peripheral neuropathy) from a prior treatment which has not resolved to at least Grade 2 or better by Cycle 1 Day 1 (C1D1).
  • - Severe hepatic dysfunction with either: a.
Total bilirubin > 2x ULN (> 3x ULN in subjects with Gilbert's syndrome [hereditary indirect hyperbilirubinemia]), and/or b. AST and/or ALT > 2.5x ULN.
  • - Severe renal dysfunction with an estimated creatinine clearance of < 15 mL/min calculated using the Cockcroft and Gault formula.
  • - Impaired hematopoietic function with either: a.
White blood cell count < 1,500/mm3, and/or b. Absolute neutrophil count < 1000/mm3, and/or c. Hemoglobin < 8.0 g/dL, and/or d. Platelet count < 100,000/mm3 (for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, platelets ≥ 75,000/mm3 are acceptable).
  • - Blood (or blood product) transfusions or blood growth factors within 7 days of C1D1.
Use of hematopoietic growth factor support is acceptable, including erythropoietin (EPO), darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag or romiplostim). However, patients must be platelet transfusion independent for > 1 week in order to be enrolled in the study.
  • - Radiation, chemotherapy or immunotherapy, or any other anticancer therapy within 2 weeks prior to C1D1, or radio-immunotherapy within 6 weeks prior to C1D1.
Patients on long-term glucocorticoids during Screening do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures, as well as for pain management.
  • - Patients with history of spinal cord compression with residual paraplegia.
  • - Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1.
  • - Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1D1.
  • - Active graft versus host disease after allogeneic stem cell transplantation.
  • - Life expectancy < 3 months.
  • - Major surgery within 4 weeks prior to C1D1.
  • - Active, unstable cardiovascular function with either: a.
Symptomatic ischemia, b. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, d. Myocardial infarction (MI) within 6 months prior to C1D1, or e. Screening 12-lead ECG showing a baseline QT interval as corrected by Bazett's formula (QTc) > 470 msec.
  • - Uncontrolled active hypertension.
  • - Venous thromboembolism within 6 months prior to C1D1 or a known inherited thrombophilia.
  • - Inability to receive either prophylactic or therapeutic anticoagulation as determined appropriate by the Investigator.
  • - Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to C1D1.
  • - Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment.
  • - Currently pregnant or breastfeeding.
Lactating females must agree not to breast feed while receiving selinexor, pomalidomide and/or clarithromycin.
  • - A serious psychiatric or medical condition which, in the opinion of the Investigator, could interfere with treatment.
  • - Hypersensitivity or contraindication to selinexor, pomalidomide, dexamethasone and/or clarithromycin.
  • - Prior exposure to a SINE compound, including selinexor.
  • - Concomitant use of any strong CYP3A4 and/or CYP1A2 inhibitors (see Appendix 1) - Unable to obtain commercial clarithromycin, pomalidomide and dexamethasone through a regular and/or specialty pharmacy.
  • - Unable or unwilling to register into the mandatory POMALYST REMSTM program and comply with its requirements.
  • - Male and female patients unwilling or unable to use effective methods of contraception throughout the study and for three months following the last dose.
Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Note that female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at Screening and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04843579
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Weill Medical College of Cornell University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jorge Monge, MD
Principal Investigator Affiliation Weill Medical College of Cornell University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Myeloma Multiple, Myeloma, Refractory Multiple Myeloma
Arms & Interventions

Arms

Experimental: Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

Selinexor • Given orally at a dose of 60 mg on days 1, 8, and 15 of a 28-day cycle. Dexamethasone Given orally at a dose of 40 mg on days 1, 8, 15 and 22 of a 28-day cycle. Subjects will receive a prescription for dexamethasone 4 mg tablets (generic). Clarithromycin Given orally at a dose of 500 mg twice a day on days 1-28 of a 28-day cycle. Subjects will receive a prescription for clarithromycin 250 or 500 mg tablets (generic) for oral administration. Pomalidomide Given orally at a dose of 4 mg daily on days 1-21 of a 28-day cycle. Subjects will receive a 21-day supply of pomalidomide 1, 2, 3, or 4 mg capsules for oral administration for each treatment cycle.

Interventions

Drug: - Selinexor

Given as 60 mg oral capsule

Drug: - Clarithromycin

Given as 500 mg oral capsule

Drug: - Pomalidomide

Given as 4 mg oral capsule

Drug: - Dexamethasone

Given as 40 mg oral capsule

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Brooklyn, New York

Status

Recruiting

Address

NewYork-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215

Site Contact

Perry Cook, MD

pec9040@nyp.org

646-962-6500

New York, New York

Status

Recruiting

Address

Weill Cornell Medicine - Multiple Myeloma Center

New York, New York, 10065

Site Contact

Kathleen Research Nurse, RN

kap9111@med.cornell.edu

646-962-6500