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

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ClinicalTrials.gov Identifier: NCT04843579
Recruitment Status : Recruiting
First Posted : April 13, 2021
Last Update Posted : January 24, 2022
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myeloma Multiple Myeloma Refractory Multiple Myeloma Drug: Selinexor Drug: Clarithromycin Drug: Pomalidomide Drug: Dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Single-Arm Study of Selinexor in Combination With Clarithromycin, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : December 29, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. Percentage of Participants With Overall Response Rate of Partial Response or Better [ Time Frame: Approximately 40 months ]
    Overall response rate will be defined as percentage of participants who achieve Partial Response or Better according to the International Myeloma Working Group response criteria


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: Approximately 24 months ]
    Adverse events will be determined by Events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The frequency of adverse events will be collected in tabular summary from when a participant consent to study until end of study or patient participant starts a new treatment.



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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT04843579


Contacts
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Contact: Kathleen Research Nurse, RN 646-962-6500 kap9111@med.cornell.edu

Locations
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United States, New York
NewYork-Presbyterian Brooklyn Methodist Hospital Recruiting
Brooklyn, New York, United States, 11215
Contact: Perry Cook, MD       pec9040@nyp.org   
Principal Investigator: Perry Cook, MD         
Weill Cornell Medicine - Multiple Myeloma Center Recruiting
New York, New York, United States, 10065
Contact: Kathleen Research Nurse, RN    646-962-6500    kap9111@med.cornell.edu   
Contact: Natalie Research Nurse, RN    646-962-6500    naa9101@med.cornell.edu   
Principal Investigator: Jorge Monge, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Karyopharm Therapeutics Inc
Investigators
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Principal Investigator: Jorge Monge, MD Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT04843579    
Other Study ID Numbers: 20-12023093
First Posted: April 13, 2021    Key Record Dates
Last Update Posted: January 24, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Clarithromycin
Dexamethasone
Pomalidomide
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
Anti-Bacterial Agents
Anti-Infective Agents