A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Conditions

• Relapsed/Refractory Diffuse Large B-cell Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Selinexor (combination therapy) — DRUG
  Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
• Selinexor (combination therapy) — DRUG
  Dose: 60 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
• Selinexor (combination therapy) — DRUG
  Dose: Selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
• Placebo matching for Selinexor (combination therapy) — DRUG
  Dose: Placebo matching for selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
• Rituximab (combination therapy) — DRUG
  Dose: 375 milligram per meter square (mg/m\^2) on Day 1; Route of administration: intravenous (IV)
• Rituximab (combination therapy) — DRUG
  Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
• Gemcitabine (combination therapy) — DRUG
  Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
• Dexamethasone (combination therapy) — DRUG
  Dose: 40 mg (20 mg if patient is more than 70 years old) on Days 1, 2, 3, and 4; Route of administration: oral or IV
• Cisplatin (combination therapy) — DRUG
  Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
• Selinexor (continuous therapy) — DRUG
  Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
• Placebo matching for Selinexor (continuous therapy) — DRUG
  Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral

Study Details

The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram \[mg\] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.

Key Dates

Start date

Sep 3, 2020

Status verified

May 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

501 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 2: Selinexor 40 mg + R-GDP
  Patients with RR DLBCL will receive combination therapy of selinexor 40 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally once weekly (QW) for each 28-day cycle until progressive disease (PD) or unacceptable toxicity.
• Experimental: Phase 2: Selinexor 60 mg + R-GDP
  Patients with RR DLBCL will receive combination therapy of selinexor 60 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
• Active Comparator: Phase 2: R-GDP
  Patients with RR DLBCL will receive R-GDP on specified days (Days 1, 2, 3, 4, and 8) for each 21-day cycle for up to 6 cycles.
• Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg
  Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
• Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo
  Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.
• Placebo Comparator: Phase 3: Placebo + R-GDP followed by Placebo
  Patients with RR DLBCL will receive combination therapy of placebo matching for selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.

Primary Outcome Measure

Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014 [ Time Frame: From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization) ]

Locations (8)

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