Study of Selinexor in Combination With Backbone Treatments or Novel Therapies In Participants With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)

Conditions

• Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Selinexor — DRUG
  Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
• Rituximab — DRUG
  Dose: 375 mg/m\^2
• Bendamustine — DRUG
  Dose: 90 mg/m\^2
• Polatuzumab Vedotin — DRUG
  Dose: 1.8 mg/kg
• Ibrutinib — DRUG
  Dose: 420, 560 mg
• Lenalidomide — DRUG
  Dose: 20, 25 mg
• Tafasitamab — DRUG
  Dose: 12 mg/kg
• Venetoclax — DRUG
  Dose: 200, 400, 600, 800 mg
• Gemcitabine — DRUG
  Dose: 1000 mg/m\^2
• Oxaliplatin — DRUG
  Dose: 100 mg/m\^2

Study Details

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.

Key Dates

Start date

Nov 18, 2020

Status verified

Sep 2025

Primary completion

Dec 31, 2025

Completion

Dec 31, 2025

Study Design

Enrollment

0 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: Selinexor with Bendamustine and Rituximab (S-BR))
  Participants will receive a dose of 40 or 60 or 80 milligrams (mg) of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an intravenous (IV) dose of bendamustine 90 milligram per square meter (mg/m\^2) on Days 1 and 2 and IV dose of rituximab 375 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
• Experimental: Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR)
  Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of polatuzumab vedotin 1.8 milligram per kilogram (mg/kg) and IV dose of rituximab 375 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
• Experimental: Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR)
  Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of polatuzumab vedotin 1.8 mg/kg and IV dose of rituximab 375 mg/m\^2 on Day 1, and IV dose of bendamustine 90 mg/m\^2 on Days 1 and 2 during primary treatment for Cycle 1 to 6.
• Experimental: Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx)
  Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1 and 3 for Cycle 1 to 6 (each cycle consists of 14 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2, IV dose of gemcitabine 1000 mg/m\^2, and Oxaliplatin IV dose of 100 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
• Experimental: Arm E: Selinexor with Ibrutinib and Rituximab (S-IR)
  Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 6 during primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2-4) during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2 on Day 1, and ibrutinib oral dose of 420 or 560 mg once daily on Day 1 to 28 during primary treatment for Cycle 1 to 6. Participants will also receive ibrutinib oral dose of 420 mg once daily at all dose levels during continuous treatment.
• Experimental: Arm F: Selinexor with Lenalidomide and Rituximab (S-LR)
  Participants will receive a dose of 40 or 60 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 6 during primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2) during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2 on Day 1, and lenalidomide oral dose of 20 mg once daily on Days 1 to 21 during primary treatment for Cycle 1 to 6. Participants will also receive lenalidomide oral dose of 20 mg on Days 1 to 21 at all dose levels during the continuous treatment.
• Experimental: Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT)
  Participants will receive a dose of 40 or 60 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 12 during primary treatment and 40 (dose level 1) then 60 mg (dose level 2) during continuous treatment (each cycle consists of 28 days). During the primary treatment, participants will also receive lenalidomide oral dose of 25 mg once daily on Days 1 to 21, and tafasitamab IV dose of 12 mg/kg on Days 1, 8, 15, and 22 for Cycle 1 to 3 and Days 1 and 15 for Cycle 4 to 12. Participants will also receive an IV dose of tafasitamab 12 mg/kg on Days 1 and 15 for all dose levels during the continuous treatment.
• Experimental: Arm H: Selinexor with Venetoclax (S-V)
  Participants will receive 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 8 and 15 for Cycle 1 to 6 of primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2-5) during continuous treatment (28 days per cycle). Participants who received 40 and 60 mg of selinexor during primary treatment will also receive oral dose of venetoclax 200 mg on Days 1 to 7 then 400 mg on Days 8 to 28 for Cycle 1; 400 mg daily for Cycle 2 to 6. Participants who received 60 and 80 mg of selinexor during primary treatment will also receive venetoclax 400 mg orally on Days 1 to 7 then 600 mg on Days 8 to 28 for Cycle 1; 600 mg daily for Cycle 2 to 6. Participants who received 80 mg selinexor during primary treatment will also receive venetoclax 400 mg orally on Days 1 to 7, then 600 mg from Days 8 to 14, then 800 mg from Day 15 to 28 for Cycle 1; 800 mg daily for Cycle 2 to 6. Participants during continuous treatment will also receive venetoclax 400 mg orally daily.

Primary Outcome Measure

Phase 1: Maximum Tolerated Dose (MTD) [ Time Frame: Within the first cycle (maximum 28 days) of treatment ]

Locations (18)

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