Selinexor Maintenance Post CAR-T Cell Therapy for Multiple Myeloma
ConditionMultiple Myeloma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
The outcomes in patients with relapsed or refractory multiple myeloma refractory to triple-therapy remain poor. These patients are eligible for chimeric antigen receptor T-cells (CAR-T), which rely on redirecting autologous T-cells to clear myeloma cells by targeting B-cell maturation antigen (BCMA). BCMA CAR-T therapy is not curative, and unlike autologous stem cell transplant, there is currently no standard for maintenance therapy post CAR-T which could potentially increase MRD rates and extend progression-free survival.
Selinexor is an exportin (XPO1) inhibitor with direct anti-tumor effect used often as an adjunct with other agents as bridging therapy prior to CAR-T. As selinexor does not affect T-cell yields or fitness, T-cell collection on selinexor for CAR-T manufacturing is safe.
The aim of this study is to evaluate the safety and toxicity of selinexor in relapsed or refractory multiple myeloma patients with high-risk features (adverse risk cytogenetics, less than complete response (CR) post CAR-T, or extramedullary disease) following BCMA CAR-T therapy. The investigators hypothesize that selinexor as maintenance therapy following CAR-T has the potential to act synergistically with CAR-T cells leading to more durable responses.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Deletion of 17p with a cancer clonal fraction (CCF) ≥20%, assessed on CD138-positive/purified plasma cells, AND/OR
TP53 mutation identified using a validated next-generation sequencing (NGS)-based assay.
Presence of t(4;14), t(14;16), or t(14;20) in combination with either gain/amplification of 1q (1q+) and/or deletion of 1p32.
Monoallelic deletion of 1p32 occurring with gain/amplification of 1q, OR
Disqualifiers
MM with active CNS involvement.
Confirmed progressive disease by IMWG after CAR-T administration.
Unresolved cytokine release syndrome (CRS) or CAR-T neurologic toxicity.
Any unresolved non-hematologic grade ≥ 3 treatment-related toxicity from CAR-T.
Trial design
Design model
Single group
Treatments tested in this trial
Selinexor
DrugSelinexor will be provided by Karyopharm Therapeutics, Inc.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: SelinexorExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Rate of non-hematologic grade ≥ 3 treatment-related adverse events (excluding conditioning and CAR-T related adverse events) according to CTCAE v 6.0
Time frame
From start of selinexor through 30 days after the last dose of selinexor (estimated to be 13 months)2
Tolerability as measured by rate of patients who received > 80% of cumulative selinexor dose during the study period
Time frame
Through completion of selinexor treatment (estimated to be 12 months)Secondary outcomes
1
Rate of MRD negativity by clonoSEQ sensitive to 10-5
Time frame
At 6 months after CAR-T infusion2
Rate of MRD negativity by clonoSEQ sensitive to 10-5
Time frame
At 12 months after CAR-T infusion3
Rate of complete response (CR) and stringent CR (sCR) by IMWG response criteria
* sCR: Stringent complete response requires all of the following: * CR as defined below * Normal free light chain ratio (0.26-1.65) * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence * CR: Complete response requires all of the following: * Negative immunofixation on the serum and urine * Normal free light chain ratio (0.26-1.65) * \<5% plasma cells in the bone marrow aspirate * Disappearance of any soft tissue plasmacytomas
Time frame
At 6 months after CAR-T infusion4
Rate of complete response (CR) and stringent CR (sCR) by IMWG response criteria
* sCR: Stringent complete response requires all of the following: * CR as defined below * Normal free light chain ratio (0.26-1.65) * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence * CR: Complete response requires all of the following: * Negative immunofixation on the serum and urine * Normal free light chain ratio (0.26-1.65) * \<5% plasma cells in the bone marrow aspirate * Disappearance of any soft tissue plasmacytomas
Time frame
At 12 months after CAR-T infusionSponsors and contacts
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Washington University School of Medicine
Lead sponsor
Karyopharm Therapeutics Inc
Collaborator
Source ClinicalTrials.gov