Study of Selinexor in Combination With Backbone Treatments or Novel Therapies In Participants With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
a study on Diffuse Large B-Cell Lymphoma Lymphoma Non-Hodgkin Lymphoma
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at Orange, California and other locations
- Dates
- study startedestimated completion
- Principal Investigator
- by Elizabeth Brem, MD
Description
Summary
This is a Phase 1/2, multicenter, open-label study to evaluate the efficacy, and safety of various combinations with selinexor in participants with RR DLBCL. The study will be conducted in two phases: Phase 1 and 2. The Phase 1 of the study will be a standard 3 + 3 dose escalation to determine the maximal tolerated dose (MTD), recommended Phase 2 dose (RP2D) for each treatment arm, and assess the dose limiting toxicities (DLTs). The Phase 2 of the study will be a dose expansion study to assess the efficacy and safety of for RP2D selected at the end of Phase 1 of the study for each treatment arm.
Official Title
A Multicenter, Phase 1/2 Study of Selinexor in Combination With Backbone Treatments or Novel Therapies in Patients With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
Keywords
Relapsed or Refractory Diffuse Large B-Cell Lymphoma Karyopharm Diffuse Large B-Cell Lymphoma DLBCL KPT-330 Selinexor Bendamustine Rituximab Polatuzumab Vedotin Gemcitabine Oxaliplatin Ibrutinib Lenalidomide Tafasitamab Venetoclax Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Bendamustine Hydrochloride ArmC: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR)
Eligibility
You can join if…
Open to people ages 18 years and up
- Participants greater than or equal to (≥) 18 years of age.
- Pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma).
- Prior lines of systemic therapy for the treatment of DLBCL:
- For Arms A, B, C, E, F, H: Participants must have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL.
- For Arm D (S-R-GemOx) participants must have received at least 1 but not more than 2 lines of systemic therapy (Documentation to be provided).
- For Arm G (S-LT) participants must have received only 1 line of systemic therapy
- Positron emission tomography (PET) positive measurable disease per the Lugano Classification 2014, having at least 1 node with longest diameter (LDi) greater than (>) 1.5 centimetres (cm) or 1 extranodal lesion with LDi >1 cm.
- Adequate bone marrow function.
- Circulating lymphocytes less than or equal to (≤) 50 * 109/L.
- Adequate liver and kidney function.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- An estimated life expectancy of >6 months at Screening.
- . Participants with primary refractory disease defined as no response or relapse within 6 months after ending first-line treatment will be allowed on study (up to 20 percentage [%] of enrolled participants in each Phase).
- . Male participants and female participants of childbearing potential must agree to use highly effective methods of contraception: Male participants must agree not to donate sperm.
- . Participants with active hepatitis B Virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 international units per milliliter (IU/mL); participants with hepatitis C Virus (HCV) are eligible if viral load is negative; participants with human immunodeficiency virus (HIV) are eligible if cluster of differentiation 4 (CD4+) T-cell counts ≥350 cells per microliter (cells/μL), viral load is negative and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
You CAN'T join if...
- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin lymphoma + NHL); Gray zone lymphoma; DLBCL transformed from Chronic Lymphocytic Leukemia (Richter Syndrome); Primary mediastinal large B-cell lymphoma (PMBCL); T-cell rich large B-cell lymphoma.
- Participants with high grade lymphoma with c-MYC, B-cell lymphoma 2 (BCL-2) and/or BCL-6 rearrangements are excluded from the Phase 1 portion of the study only.
- Previous treatment with selinexor or other XPO1 inhibitors.
- Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to Cycle 1 Day 1 (C1D1). Low dose steroids <30 mg prednisone (or equivalent) are permitted; and palliative radiotherapy.
- Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing or strong CYP3A inducers ≤14 days prior to Day 1 dosing.
- Major surgery <14 days of C1D1.
- Autologous stem cell transplant (SCT) <100 days or allogeneic SCT <180 days prior to C1D1 or active graft-versus-host disease after allogeneic SCT (or cannot discontinue graft versus host disease [GVHD] treatment or prophylaxis).
- Prior chimeric antigen receptor T cell (CAR-T cell) infusion at any time (Phase 1 only); prior CAR-T cell infusion ≤120 days prior to C1D1 (Phase 2 only).
The following are Arm Specific exclusion criteria:
- Arm B (S-PR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
- . Arm C (S-PBR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
- . Arm D (S-R-GemOx): Neuropathy Grade 2≥ (CTCAE, v5.0) interstitial lung disease or pulmonary fibrosis.
Locations
- University of California Irvine
not yet accepting patients
Orange California 92868 United States - California Cancer Associates for Research and Excellence
accepting new patients
Encinitas California 92024 United States
Lead Scientist at UC Irvine
- Elizabeth Brem, MD
Assistant Health Sciences Professor, Medicine. Authored (or co-authored) 9 research publications.
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Karyopharm Therapeutics Inc
- ID
- NCT04607772
- Phase
- Phase 1/2
- Study Type
- Interventional
- Last Updated