Selinexor and Lenalidomide for Consolidation and Maintenance Treatment in Multiple Myeloma Post-transplant

NCT05820763 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 202306068
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II clinical trial studies the addition of selinexor to lenalidomide in patients with multiple myeloma following transplant. Selinexor is an oral medication approved for use in patients with multiple myeloma following failure of other regimens, and lenalidomide is an oral medication approved for use in patients with multiple myeloma following transplant. This study is testing if the combination of selinexor and lenalidomide is more effective than lenalidomide alone in this setting.

Conditions

Multiple Myeloma; Myeloma-Associated Amyloidosis

Keywords

symptomatic multiple myeloma; myeloma post-AHCT; myeloma post-transplant; Multiple myeloma with amyloid deposition; Multiple Myeloma; post-transplant maintenance; Minimal residual disease

Outcome Measures

Primary Outcomes (2)

• Rate of Minimal Residual Disease (MRD) negativity

  Defined by rate of MRD negativity using clonoSEQ MRD® assay at a sensitivity of 10\^-5. MRD negativity is defined as 0 residual clonal cells in a bone marrow biopsy sample.

  At the end of consolidation treatment (at the end of 4 cycles (each cycle is 28 days)

• Rate of Minimal Residual Disease (MRD) negativity

  Defined by rate of MRD negativity using clonoSEQ MRD® assay at a sensitivity of 10\^-5. MRD negativity is defined as 0 residual clonal cells in a bone marrow biopsy sample.

  12 months from study treatment initiation

Secondary Outcomes (2)

• Rate of partial response or better

  12 months from study treatment initiation

• Progression-free survival (PFS)

  12 months from study treatment initiation

Study Arms (2)

Consolidation: Selinexor, Lenalidomide, and Dexamethasone

EXPERIMENTAL

Consolidation will begin between Days 80 and 140 following standard of care autologous hematopoietic stem cell transplant and the treatment will consist of selinexor, lenalidomide, and dexamethasone for 4 28-day cycles.

Drug: Selinexor; Drug: Lenalidomide; Drug: Dexamethasone

Maintenance: Selinexor and Lenalidomide

EXPERIMENTAL

Maintenance will consist of selinexor and lenalidomide for a maximum of 8 28-day cycles.

Drug: Selinexor; Drug: Lenalidomide

Interventions

Selinexor DRUG

Selinexor is administered by mouth on Days 1, 8, 15, and 22 at a dose of 60 mg during the four cycles of consolidation. Selinexor is then decreased to 40 mg and administered by mouth on Days 1, 8, 15, and 22 for up to 8 cycles of maintenance therapy.

Also known as: EXPOVIO, KPT-330

Consolidation: Selinexor, Lenalidomide, and Dexamethasone; Maintenance: Selinexor and Lenalidomide

Lenalidomide DRUG

Lenalidomide is administered by mouth daily on Days 1 to 21 at a dose of 10 mg during the first three cycles of consolidation, and then titrated up to 15 mg on Days 1 to 21 for the fourth cycle of consolidation. Lenalidomide 15 mg by mouth daily on Days 1 to 21 can be continued for up to 8 cycles of maintenance therapy. For patients with baseline renal dysfunction, the starting dose of lenalidomide will be 2.5 mg or 5 mg by mouth daily on Days 1 to 21. Patients may titrate up per physician discretion.

Also known as: Revlimid

Consolidation: Selinexor, Lenalidomide, and Dexamethasone; Maintenance: Selinexor and Lenalidomide

Dexamethasone DRUG

Dexamethasone is administered by mouth on Days 1, 8, 15, and 22 at a dose of 20 mg during all four cycles of consolidation only.

Also known as: Decadron

Consolidation: Selinexor, Lenalidomide, and Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years of age at time of enrollment.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
• Histologically confirmed diagnosis of multiple myeloma that is symptomatic. Patients with multiple myeloma with local amyloid deposition in the bone marrow are eligible.
• Patients must have undergone lenalidomide-based induction regimen.
• Patient must have undergone AHCT within 80 to 140 days prior to C1D1 for MM.
• Patient must be MRD-positive (per 10\^-5 threshold) using clonoSEQ MRD® assay on bone marrow biopsy prior to study enrollment.
• Patient must have achieved very good partial response or better per IMWG response criteria prior to study enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 K/cumm.
• Platelet count ≥ 100 K/cumm (patients for whom \<50% of bone marrow nucleated cells are plasma cells) or ≥50 K/cumm (patients for whom ≥50% of bone marrow nucleated cells are plasma cells).; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before C1D1.
• Hemoglobin ≥ 8.5 g/dL without blood transfusion within 7 days before C1D1.
• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN), patients with Gilbert's syndrome must have a total bilirubin of \< 3 x ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN.
• Calculated creatinine clearance ≥ 15 mL/min per Cockcroft and Gault formula.

You may not qualify if:

• Patients with lenalidomide-refractory disease during induction.
• Prior receipt of selinexor or another XPO1 inhibitor previously.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Tandem autologous transplantation.
• History of plasma cell leukemia or MM CNS involvement.
• Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma from Day +28 post-transplant through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.).
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Prior organ transplant requiring immunosuppressive therapy.
• Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 IU/ml prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed. Subjects with Human Immunodeficiency Virus (HIV) who have CD4+ T-cell counts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections in the last year are allowed.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
• Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
• Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma with local amyloid deposition in the bone marrow).
• Active, unstable cardiovascular function, as indicated by the presence of:
• Symptomatic ischemia, or

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Karyopharm Therapeutics Inc: collaborator

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

selinexor; Lenalidomide; Dexamethasone; Calcium Dobesilate

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; Neoplastic Processes; 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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Mark Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will initially receive 4 cycles of consolidation triplet therapy followed by 8 cycles of maintenance doublet therapy.

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: April 20, 2023
• Study Start: January 5, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will be available immediately following publication, no end date.
• Access Criteria: Researchers who provide a methodologically sound proposal for any purpose may request data. Proposal should be directed to markschroeder@wustl.edu. To gain access, data requesters will need to sign a data access agreement.