Study of Selinexor (KPT- 330), Lenalidomide, & Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

NCT02389543 | Withdrawn Phase 1

• 1 other identifier: KCP-330-011
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2).

Conditions

Multiple Myeloma

Keywords

KPT-330; Selinexor; Multiple Myeloma; Relapsed/refractory; Lenalidomide; Dexamethasone; Karyopharm

Outcome Measures

Primary Outcomes (2)

• Determine maximum tolerated dose (MTD)

  Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety

  12 months

• Overall response rate (ORR)

  According to the International Myeloma Working Group \[IMWG\] criteria, Overall Response Rate (ORR) includes: stringent complete response \[sCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\]

  12 months

Study Arms (2)

A: Selinexor (1x/week), Lenalidomide, & Dexamethasone

EXPERIMENTAL

Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (\~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (\~60 mg/m2) and evaluated for MTD, tolerability and efficacy.

Drug: Selinexor; Drug: Lenalidomide; Drug: Dexamethasone

B: Selinexor (2x/week), Lenalidomide, & Dexamethasone

EXPERIMENTAL

Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (\~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (\~45 mg/m2) and evaluated for MTD, tolerability and efficacy.

Drug: Selinexor; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Selinexor DRUG

Two different dosing schedules will be tested, once weekly and twice weekly. If the selinexor 80 mg dose is tolerated, the dose will be increased to 100 mg.

Also known as: KPT-330

A: Selinexor (1x/week), Lenalidomide, & Dexamethasone; B: Selinexor (2x/week), Lenalidomide, & Dexamethasone

Lenalidomide DRUG

In both arms, lenalidomide will be started at 15 mg/day (Dose Level 1) and, if tolerated per DLT criteria, will be escalated to 25 mg/day (Dose Level 2).

A: Selinexor (1x/week), Lenalidomide, & Dexamethasone; B: Selinexor (2x/week), Lenalidomide, & Dexamethasone

Dexamethasone DRUG

Dexamethasone will be given in combination with each dose of selinexor on the once weekly treatment arm. For the twice weekly arm dexamethasone will be given in combination with each dose of selinexor and will also be given without selinexor on Days 22 and 24.

A: Selinexor (1x/week), Lenalidomide, & Dexamethasone; B: Selinexor (2x/week), Lenalidomide, & Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM.
• Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
• Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease.

You may not qualify if:

• Smoldering MM.
• Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Active MM involving the central nervous system (CNS).

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

selinexor; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: July 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: February 1, 2018
• Last Updated: January 26, 2023

Record last verified: 2023-01