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Monoclonal Antibodies

Combination Therapies with Selinexor for Multiple Myeloma (STOMP Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Karyopharm Therapeutics Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age greater than or equal to (≥) 18 years at the time of informed consent

Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to less than or equal (≤) Grade 2 by C1D1

Must not have

Documented active systemic amyloid light chain amyloidosis

MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial will assess the efficacy and safety of 10 different combination therapies in 11 arms for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM).

Who is the study for?

Adults over 18 with symptomatic multiple myeloma, either newly diagnosed or relapsed/refractory, can join. They must have measurable disease and be in good enough health to swallow pills and handle treatment side effects. Pregnant women, those with severe liver/kidney issues, recent major surgery patients, or individuals with certain infections or heart problems cannot participate.

What is being tested?

The trial is testing Selinexor combined with other drugs like dexamethasone and chemotherapy agents in different mixtures across 11 groups for treating multiple myeloma. Some groups are closed to new participants. The study includes initial phases to determine safe dosages followed by expansions to assess effectiveness.

What are the potential side effects?

Potential side effects include digestive issues that could affect tablet absorption, blood disorders requiring transfusions or growth factors, nerve pain if previously experienced at a high level (for specific arms), eye conditions from certain drug combinations (Arm 10), and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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Any side effects from past treatments have mostly gone away.

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I have symptoms from my multiple myeloma.

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I can take care of myself but might not be able to do heavy physical work.

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I am a woman who can have children and my pregnancy test was negative.

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My myeloma has returned or didn't respond to treatment and can be measured.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with active systemic light chain amyloidosis.

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My multiple myeloma does not produce M-protein or light chains.

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I can swallow tablets and don't have issues absorbing medication.

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I cannot take strong CYP3A4 inhibitors due to my current medications.

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I am experiencing complications from a stem cell transplant.

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My condition is smoldering multiple myeloma.

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I am HIV positive.

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I have active plasma cell leukemia.

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I have not had major surgery in the last 4 weeks.

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I do not have an active infection needing IV drugs within the last week.

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I have previously been treated with a SINE compound like selinexor.

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I had my own stem cell transplant less than a month ago, or a donor's less than 3 months ago.

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My heart condition is currently unstable.

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I have an active hepatitis A, B, or C infection.

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I have a corneal condition, but it's only mild punctate keratopathy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1 (Dose-escalation): Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor

Phase 1 (Dose-escalation): Maximum Plasma Concentration (Cmax) of Selinexor

Phase 1 (Dose-escalation): Maximum Tolerated Dose (MTD)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: 9: Selinexor, Low-dose DEX, Pomalidomide and Elotuzumab (SPEd)Experimental Treatment4 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 9.1: SEL 20/40/60 mg PO once weekly; DEX 28/20 mg PO twice weekly; POM 4 mg PO QD Days 1-21; Elotuzumab (ELO) 10/20 mg/kg IV will be given once weekly on Days 1,8, 15 and 22 of Cycles 1-2. Starting on Cycle 3 and continuing for future cycles, elotuzumab will be dosed at 20 mg/kg on Day 1 of each cycle only. Cohort 9.3: Selinexor, Dexamethasone, Pomalidomide and Elotuzumab will be dosed at RP2D-9.

Group II: 8: Selinexor, Low-dose dexamethasone, and Ixazomib (SNd)Experimental Treatment4 Interventions

PK Run-in Period: Selinexor \& Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 8.1: SEL 40/60/80/100 mg PO once weekly; DEX 20 mg PO twice weekly; IXA 3/4 mg PO once weekly. Cohort 8.3: Selinexor, Dexamethasone and Ixazomib will be dosed at RP2D-8.

Group III: 7: Selinexor, Low-dose DEX and Lenalidomide (SRd) in NDMMExperimental Treatment3 Interventions

Each cycle is of 28 days Cohort 7.1: SEL 40/60/80 mg PO once weekly; DEX 40 mg PO once weekly; LEN 25 mg PO Days 1-21. Cohort 7.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-7.

Group IV: 6: Selinexor, Low-dose dexamethasone, and Carfilzomib (SKd)Experimental Treatment4 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 6.1: SEL 40/60/80/100 mg PO once weekly on days 1, 8, 15, and 22; DEX 40 mg IV or PO once weekly; Carfilzomib (CAR) 56 or 70 mg/m\^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.2: SEL 60/80/100 mg PO once weekly on days 1, 8, and 15; DEX 40 mg IV or PO once weekly; CAR 56 or 70 mg/m\^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.3: Selinexor, Dexamethasone and Carfilzomib will be dosed at RP2D-6.

Group V: 5: Selinexor, Low-dose dexamethasone, and Daratumumab (SDd)Experimental Treatment3 Interventions

Each cycle is of 28 days Cohort 5.1: SEL 80/100 mg PO once weekly; DEX 40 mg once weekly (IV or PO); DARA: 16 mg/kg IV infusion Cycle 1-2: Once weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.2: SEL: 60 mg PO twice weekly; DEX: 40 mg weekly (IV or PO); DARA: 16 milligram per kilogram (mg/kg) IV infusion Cycle 1-2: Once. weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.3: Selinexor, Dexamethasone and Daratumumab will be dosed at RP2D-5.

Group VI: 4:Selinexor, Low-dose dexamethasone, Pomalidomide, Velcade (SPVd)Experimental Treatment5 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patients will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days. Cohort 4.1: SEL 40/60 mg PO once weekly; DEX 40 mg PO once weekly; POM 4 mg PO Days 1-21; BOR 1.3 mg/m\^2 subcutaneous (SC) once weekly. Cohort 4.3: Selinexor, Dexamethasone, Pomalidomide, Velcade (Bortezomib) will be dosed at RP2D-4.

Group VII: 3: Selinexor, Low-dose DEX, and Lenalidomide (SRd) in RRMMExperimental Treatment3 Interventions

Each cycle is of 28 days Cohort 3.1: SEL 40/60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Lenalidomide (LEN) 15/25 mg PO Days 1-21. Cohort 3.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; LEN 15/25 mg PO Days 1-21. Cohort 3.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-3.

Group VIII: 2: Selinexor, Low-dose Dexamethasone and Bortezomib (SVd)Experimental Treatment3 Interventions

Each cycle is of 35 days Cohort 2.1: SEL 60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Bortezomib (BOR) 1.3 milligram per meter square (mg/m\^2) subcutaneous (SC) once weekly. Cohort 2.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; BOR 1.3 mg/m\^2 subcutaneous (SC) once weekly. Cohort 2.3: Selinexor, Dexamethasone and Bortezomib will be dosed at RP2D-2.

Group IX: 1: Selinexor, Low-dose Dexamethasone and Pomalidomide (SPd)Experimental Treatment3 Interventions

Each cycle is of 28 days Cohort 1.1: Selinexor (SEL) 60/80/100 mg orally (PO) once weekly (QW); Dexamethasone (DEX) 40 mg PO once weekly; Pomalidomide (POM) 2/3/4 mg PO Days 1-21. Cohort 1.2: SEL 40/60/80 mg PO twice weekly (BIW); DEX 20 mg PO twice weekly; POM 3/4 mg PO Days 1-21. Cohort 1.3: Selinexor, Dexamethasone and Pomalidomide will be dosed at RP2D-1. Cohort 1.4: SEL 40 mg PO QW; DEX 40 mg PO QW; POM 4mg PO once daily (QD) Days 1-21.

Group X: 12. Selinexor + dexamethasone + mezigdomide (SMd)Experimental Treatment3 Interventions

The dose of selinexor will be formally escalated from 40 mg QW to 60 mg QW in combination with mezigdomide 0.6 mg daily. Mezigdomide dosing may be de-escalated as per 3+3 criteria to 0.3 mg or escalated to 1.0 mg. The dose level that passes DLT evaluation will be considered the MTD for the cohort.

Group XI: 11. Selinexor, Dexamethasone, Pomalidomide, and Daratumumab (SDPd)Experimental Treatment4 Interventions

Each Cycle is of 28 days Cohort 11.1 SEL 40/60 mg PO once weekly on Days 1, 8, and 15; DEX total 40 mg weekly (IV or PO) single or divided doses on Days 1, 8, 15, and 22; POM 4 mg PO QW Days 1-21; DARA 16 mg/kg IV or SC QW on Days 1, 8, 15 and 22 of Cycles 1-2 and on Days 1 and 15 of Cycles 3-6, Day 1 of every Cycle greater than (\>6). Cohort 11.3 Selinexor, Dexamethasone, Pomalidomide, and Daratumumab will be dosed at RP2D-11.

Group XII: 10. Selinexor, Dexamethasone, and Belantamab Mafodotin (SBd)Experimental Treatment3 Interventions

Each cycle is of 21 days Cohort 10.1: SEL 40/60/80 mg PO once weekly on Days 1, 8, and 15; DEX 40 mg PO QW on Days 1, 8, and 15; Belantamab Mafodotin (BEL) 2.5 mg/kg IV infusion every 3 weeks (Q3W) Day 1 of each cycle. Cohort 10.3: Selinexor, Dexamethasone, and Belantamab Mafodotin will be dosed at RP2D-10.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ixazomib

2017

Completed Phase 4

~3510

Mezigdomide

2023

Completed Phase 1

~40