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

NCT04843579 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-12023093
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Myeloma Multiple; Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response Rate of Partial Response or Better

  ORR is defined as participants who experience a partial response, very good partial response, complete response, or stringent complete response per International Myeloma Working Group Criteria (IMWG) 2016 criteria. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry. Partial Response is ≥50% reduction of serum M-protein plus reduction in 24 hour urinary M-protein by ≥90% or to \<200 mg per 24 h. Very Good Partial Response is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hr.

  Until disease progression; the maximum time any participant was followed for ORR was 287 days

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  Adverse events were collected from time of informed consent until 30 days after the last day of study drug administration for each participant. The maximum period that AEs were collected for a participant was 300 days.

Study Arms (1)

Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Selinexor DRUG

Given as 60 mg oral capsule

Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

Clarithromycin DRUG

Given as 500 mg oral capsule

Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

Pomalidomide DRUG

Given as 4 mg oral capsule

Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

Dexamethasone DRUG

Given as 40 mg oral capsule

Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (2)

NewYork-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medicine - Multiple Myeloma Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

selinexor; Clarithromycin; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

The statistical analysis plan (and associated statistical power) was based on an expected sample size of 26 participants. As only 4 participants enrolled, this reduced sample size was not sufficient for the statistical analysis plan as written, and, therefore, only descriptive statistics for the response proportions can be presented for the study.

Results Point of Contact

• Title: Multiple Myeloma Program Manager
• Organization: Weill Cornell Medicine

hyk4001@med.cornell.edu

646-962-9376

Study Officials

• Jorge Monge, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2021
• First Posted: April 13, 2021
• Study Start: December 29, 2021
• Primary Completion: November 30, 2022
• Study Completion: December 30, 2022
• Last Updated: October 25, 2023
• Results First Posted: October 25, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)