NCT02343042

Selinexor and Backbone Treatments of Multiple Myeloma Patients

A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma and Newly Diagnosed Multiple Myeloma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Karyopharm Therapeutics Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are: * Arm 1: Selinexor + dexamethasone + pomalidomide (SPd); enrollment complete * Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete * Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete * Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd); enrollment complete * Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete * Arm 6: Selinexor + dexamethasone + carfilzomib (SKd); enrollment complete * Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM; enrollment complete * Arm 8: Selinexor + dexamethasone + ixazomib (SNd); enrollment complete * Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd); enrollment complete * Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd); enrollment complete * Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd); enrollment complete * Arm 12: Selinexor + dexamethasone + mezigdomide (SMd); actively recruiting Selinexor pharmacokinetics: * PK Run-in (Days 1-14): Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 \[SPVd\], Arm 6 \[SKd\], Arm 8 \[SNd\], Arm 9 \[SPEd\], Arm 10 \[SBd\], and Arm 11 \[SDPd\]) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor. This run-in period does not apply to Arm 12 (SMd).

Detailed description

This is a multi-center, open-label, clinical study with Dose Escalation (Phase 1) and Expansion (Phase 2) to independently assess the MTD, efficacy , and safety of 11 combination therapies in 12 arms in patients with RRMM and NDMM. Patients will be assigned to treatment arms based on their diagnoses and treatment histories. For 9 patients, a PK Run-in period will precede Cycle 1 (DLT evaluation) to assess selinexor PK when co-administered with a strong CYP3A4 inhibitor. In the Dose Escalation Phase (Phase 1): (a) in Arm 1 (SPd), Arm 2 (SVd), and Arm 3 (SRd in RRMM), patients will be randomized to either QW or BIW selinexor dosing cohorts; (b) in Arm 5 (SDd), patients will be sequentially assigned in blocks of 3 to either QW or BIW selinexor dosing; (c) in Arm 4 (SPVd), Arm 6 (SKd), Arm 7 (Srd in NDMM), Arm 8 (SNd), Arm 9 (SPEd), Arm 10 (SBd), Arm 11 (SDPd), and Arm 12 (SMd) patients will be assigned to QW selinexor dosing. Cohort 1.4 is included from Version 10 to study safety and tolerability of SPd with selinexor 40 mg QW, is lower than RP2D (ie, selinexor 60 mg QW) in combination with pomalidomide 4 mg. Cohort 1.4 is a different expansion cohort from the one with RP2D (ie, Cohort 1.3). In Cohort 1.4, 20 patients will be enrolled in total. Starting in protocol Version 8.0, patients enrolled to the Dose Escalation Phase of Arm 4 (SPVd), Arm 6 (SKd), Arm 8 (SNd), Arm 9 (SPEd), Arm 10 (SBd), and Arm 11 (SDPd) will first be enrolled to a 14-day PK Run-in period (selinexor +/- clarithromycin) until 9 patients have been enrolled. During this 14-day PK Run-in period, selinexor 40 milligrams (mg) will be administered alone on Day 1, clarithromycin 500 mg twice daily (BID) will be administered on Days 2-8, and selinexor 40 mg will again be administered on Day 8 with the morning clarithromycin dose. Blood samples for PK analysis will be collected pre-dose and 1 (± 10 min), 1.5 (± 10 min), 2 (± 10 min), 3 (± 10 min), 4 (± 10 min), 5 (± 10 min), 6 (± 10 min), 8 (± 10 min), and 24 h (± 30 min) hours after selinexor is dosed on Day 1 (without clarithromycin) and Day 8 (with clarithromycin). Patients will then proceed to the DLT evaluation period that will begin after the completion of the 14-day PK Run-in period; this day will be designated as Cycle 1 Day 1 (C1D1) in the Dose Escalation Phase. Starting in protocol v12, in Arm 12 (SMd) additional PK sampling for mezigdomide will be collected concurrently with selinexor on Cycle 1 Day 1 (C1D1) at 2,4, and 6 hrs post-mezigdomide/selinexor dose; additional mezigdomide PK samples will be collected pre-mezigdomide dose on Days 8 and 15 of Cycles 1 and 2.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Selinexor	Oral tablets
DRUG	Dexamethasone	Oral tablets
DRUG	Lenalidomide	Oral capsule
DRUG	Pomalidomide	Oral tablets
DRUG	Bortezomib	Subcutaneous Injection (single use vial)
DRUG	Daratumumab	Intravenous Infusion
DRUG	Carfilzomib	Intravenous infusion
DRUG	Ixazomib	Oral capsule
DRUG	Elotuzumab	Intravenous infusion
DRUG	Clarithromycin	Tablets
DRUG	Belantamab Mafodotin	Intravenous infusion
DRUG	Mezigdomide	Oral Capsules

Timeline

• Start date: 2015-10-01
• Primary completion: 2027-04-01
• Completion: 2027-04-01
• First posted: 2015-01-21
• Last updated: 2025-12-22

Locations

25 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study