Genetically Risk-Stratified Venetoclax, Ibrutinib, Rituximab (± Navitoclax) in Relapsed/Refractory Mantle Cell Lymphoma

Conditions

• Mantle Cell Lymphoma Refractory

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ibrutinib — DRUG
  560 mg daily continuously
• Venetoclax — DRUG
  Oral daily. Dose escalation every 7 days (if no TLS) 20mg, 50mg, 100mg, 200mg and 400mg
• Navitoclax — DRUG
  Oral daily. Dose-escalation every 14 days (if plt \>75x10\^9/L) 50mg, 100mg, 150mg, and 200mg (target dose)
• Rituximab — DRUG
  375mg/m2, intravenous. To be given on day 1 of weeks 1, 2, 3, 4 of C1 and day 1 of C2-C8

Study Details

This is an open label, multi-centre, phase II study in which RR MCL patients will be genetically risk-stratified into Standard risk (no 9p21.1-24.3 loss, no SMARCA2 or SMARCA4 mut/del) and High risk (9p21.1-24.3 loss, SMARCA2 and/or SMARCA4 mut/del). Patients without the high-risk mutations will be treated with ibrutinib, rituximab and venetoclax. Patients with the high-risk mutations will be treated with ibrutinib, rituximab, venetoclax and navitoclax.

Key Dates

Start date

Sep 7, 2023

Status verified

Aug 2024

Primary completion

Jun 1, 2026

Completion

Jun 1, 2029

Study Design

Enrollment

40 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Standard-Risk Cohort
  Patients without the high-risk mutations (no 9p21.1-24.3 loss, no SMARCA2 or SMARCA4 mut/del) will be treated with ibrutinib, rituximab and venetoclax.
• Experimental: High-Risk Cohort
  Patients with the high-risk mutations (9p21.1-24.3 loss, SMARCA2 and/or SMARCA4 mut/del) will be treated with ibrutinib, rituximab, venetoclax and navitoclax.

Primary Outcome Measure

Depth of MCL response to venetoclax and ibrutinib in combination with rituximab as determined by MRD at 16 weeks. [ Time Frame: 2.5 years ]