Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Ayad Hamdan
Photo of Ayad Hamdan
Ayad Hamdan

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

  1. Participants greater than or equal to (≥) 18 years of age.
  2. Pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma).
  3. Prior lines of systemic therapy for the treatment of DLBCL:
  4. 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.
  5. 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).
  6. For Arm G (S-LT) participants must have received only 1 line of systemic therapy
  7. 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.
  8. Adequate bone marrow function.
  9. Circulating lymphocytes less than or equal to (≤) 50 * 109/L.
  10. Adequate liver and kidney function.
  11. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  12. An estimated life expectancy of >6 months at Screening.
  13. . 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).
  14. . 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.
  15. . 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...

  1. 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.
  2. 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.
  3. Previous treatment with selinexor or other XPO1 inhibitors.
  4. 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.
  5. 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.
  6. Major surgery <14 days of C1D1.
  7. 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).
  8. 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:

  1. Arm B (S-PR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
  2. . Arm C (S-PBR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
  3. . Arm D (S-R-GemOx): Neuropathy Grade 2≥ (CTCAE, v5.0) interstitial lung disease or pulmonary fibrosis.

Locations

  • UC San Diego Moores Cancer Center
    La Jolla California 92093 United States
  • Scripps MD Anderson Cancer Center
    San Diego California 92103 United States

Lead Scientist at UCSD

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Karyopharm Therapeutics Inc
ID
NCT04607772
Phase
Phase 1/2
Study Type
Interventional
Last Updated