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Selinexor and Backbone Treatments of Multiple Myeloma Patients

ConditionMultiple Myeloma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKaryopharm Therapeutics Inc

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent signed in accordance with federal, local, and institutional guidelines.

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

Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.

Symptomatic MM, based on IMWG guidelines.

Disqualifiers

Smoldering MM.

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

Documented active systemic amyloid light chain amyloidosis.

Active plasma cell leukemia.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Selinexor

    Drug

    Oral tablets

  • Dexamethasone

    Drug

    Oral tablets

  • Lenalidomide

    Drug

    Oral capsule

  • Pomalidomide

    Drug

    Oral tablets

  • Bortezomib

    Drug

    Subcutaneous Injection (single use vial)

  • Daratumumab

    Drug

    Intravenous Infusion

  • Carfilzomib

    Drug

    Intravenous infusion

  • Ixazomib

    Drug

    Oral capsule

  • Elotuzumab

    Drug

    Intravenous infusion

  • Clarithromycin

    Drug

    Tablets

  • Belantamab Mafodotin

    Drug

    Intravenous infusion

  • Mezigdomide

    Drug

    Oral Capsules

Treatment groups

300 Participants
are divided into 12 treatment groups

12

Treatment groups

See each treatment group below.

Group A: 1: Selinexor, Low-dose Dexamethasone and Pomalidomide (SPd)Experimental treatment 3 interventions
Group B: 2: Selinexor, Low-dose Dexamethasone and Bortezomib (SVd)Experimental treatment 3 interventions
Group C: 3: Selinexor, Low-dose DEX, and Lenalidomide (SRd) in RRMMExperimental treatment 3 interventions
Group D: 4:Selinexor, Low-dose dexamethasone, Pomalidomide, Velcade (SPVd)Experimental treatment 5 interventions
Group E: 5: Selinexor, Low-dose dexamethasone, and Daratumumab (SDd)Experimental treatment 3 interventions
Group F: 6: Selinexor, Low-dose dexamethasone, and Carfilzomib (SKd)Experimental treatment 4 interventions
Group G: 7: Selinexor, Low-dose DEX and Lenalidomide (SRd) in NDMMExperimental treatment 3 interventions
Group H: 8: Selinexor, Low-dose dexamethasone, and Ixazomib (SNd)Experimental treatment 4 interventions
Group I: 9: Selinexor, Low-dose DEX, Pomalidomide and Elotuzumab (SPEd)Experimental treatment 4 interventions
Group J: 10. Selinexor, Dexamethasone, and Belantamab Mafodotin (SBd)Experimental treatment 3 interventions
Group K: 11. Selinexor, Dexamethasone, Pomalidomide, and Daratumumab (SDPd)Experimental treatment 4 interventions
Group L: 12. Selinexor + dexamethasone + mezigdomide (SMd)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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

MTD for once weekly and twice weekly selinexor dose cohorts in the 11 Arms will be evaluated.

Time frame
12 months
2

Phase 1 (Dose-escalation): Recommended Phase-2 dose (RP2D)

RP2D for each Arm will be determined.

Time frame
12 months
3

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

Cmax of selinexor over a dosing interval when given with and without clarithromycin.

Time frame
Pre-dose, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post-dose on Day 1 (without clarithromycin) and Day 8 (with clarithromycin)
4

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

Total exposure of selinexor in the blood (AUC0-last) from the time of dosing to the last measurable concentration collected when given with and without clarithromycin.

Time frame
Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post-dose on Day 1 (without clarithromycin) and Day 8 (with clarithromycin)

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Karyopharm Therapeutics Inc

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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