Clinical Trials /

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

NCT04843579

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 20-12023093
  • NCT ID: NCT04843579

Conditions

  • Myeloma Multiple
  • Myeloma
  • Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
SelinexorSelinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)
ClarithromycinSelinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)
PomalidomideSelinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)
DexamethasoneSelinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

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.

Trial Arms

NameTypeDescriptionInterventions
Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)ExperimentalSelinexor • 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.
  • Selinexor
  • Clarithromycin
  • Pomalidomide
  • Dexamethasone

Eligibility 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.
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Overall Response Rate of Partial Response or Better
Time Frame:Approximately 40 months
Safety Issue:
Description: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

Measure:Number of Participants with Adverse Events
Time Frame:Approximately 24 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

August 27, 2021