A Study of Ibrutinib With Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (VEGA)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Lymphoma, Mantle-Cell

Treatments: Drug: Rituximab; Drug: Ibrutinib; Drug: Bortezomib; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05564052

CR109252

2023-503618-64-00 (Registry Identifier)

2022-000364-21 (EudraCT Number)

54179060MCL3004 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to provide continued access to treatment for participants who continue to benefit from treatment.

Full description

Mantle cell lymphoma (MCL) is an uncommon and incurable clinicopathologic subtype of B-cell non-Hodgkin Lymphoma (NHL). Ibrutinib is a first-in-class potent, orally administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTKi) for the treatment of B-cell malignancies and chronic graft-versus-host disease. The primary hypothesis of the study is to provide continued access to treatment for participants who continue to benefit from treatment. The study will include a screening phase (up to 30 days prior to randomization), a treatment phase (from randomization until study treatment discontinuation). safety assessments include adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination. The Phase 2 exploratory objectives and endpoints of characterization of pharmacokinetic and pharmacodynamic of ibrutinib may continue to be evaluated using blood samples already collected. The total duration of the study will be up to 2 years 1 month.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• At least 1 prior treatment regimen for mantle cell lymphoma (MCL) excluding inhibitor of Bruton's tyrosine kinase (BTKi)
• Documented disease progression or relapse following the last anti-MCL treatment
• At least 1 measurable site of disease on cross-sectional imaging that is greater than or equal to (>=) 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per computed tomography (CT)
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1

Exclusion criteria

• Prior therapy with ibrutinib or other BTK inhibitor
• Prior treatment with both lenalidomide and bortezomib. Prior treatment with only 1 of these therapies is allowed
• Major surgery within 4 weeks of randomization
• Concurrent enrollment in another therapeutic investigational study
• Known central nervous system lymphoma
• History of stroke or intracranial hemorrhage within 6 months prior to randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

36 participants in 4 patient groups

Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib)

Experimental group

Description:

Participants will receive rituximab 375 milligrams per meter square (mg/m\^2) intravenously (IV) on Day 1 of Cycles 1 to 6 with ibrutinib 560 milligrams (mg) orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Treatment:

Drug: Ibrutinib

Drug: Rituximab

Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib)

Experimental group

Description:

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 420 mg orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Treatment:

Drug: Ibrutinib

Drug: Rituximab

Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib)

Experimental group

Description:

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 140 mg orally, twice daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Treatment:

Drug: Ibrutinib

Drug: Rituximab

Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib)

Experimental group

Description:

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 (each cycle length is 21 or 28 days) with physician's choice of either lenalidomide 20 mg orally, once daily from Day 1 through Day 21 of 28-day cycle or bortezomib 1.3 mg/m\^2 IV or subcutaneously (SC) on Days 1, 4, 8 and 11 of a 21-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Lenalidomide

Drug: Bortezomib

Drug: Rituximab