A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations

Conditions

• Chronic Lymphocytic Leukemia in Relapse
• Chronic Lymphocytic Leukemia in Remission

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ibrutinib + Venetoclax 15 cycles — DRUG
  Cycle 1 + 2: 420 mg ibrutinib, day 1-28 \| Cycle 3: 420 mg ibrutinib, day 1-28 \| 20 mg venetoclax, day 1-7 \| 50 mg venetoclax, day 8-14 \| 100 mg venetoclax, day 15-21 \| 200 mg venetoclax, day 22-28 \| Cycle 4-15: 420 mg ibrutinib, day 1-28 + 400mg venetoclax, day 1-28
• Ibrutinib until progression/relapse — DRUG
  420mg ibrutinib daily until progression/relapse
• Possible reinitiation treatment: Ibrutinib + Venetoclax 12 cycles — DRUG
  Cycle 1: 420 mg ibrutinib \| 20 mg venetoclax, day 1-7 \| 50 mg venetoclax, day 8-14 \| 100 mg venetoclax, day 15-21 \| 200 mg venetoclax, day 22-28 \| cycles 2-12: 420 mg ibrutinib, day 1-28 + 400 mg venetoclax, day 1-28

Study Details

The aim of the current trial is to evaluate if combination treatment with venetoclax + ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (RR CLL) can lead to MRD negativity, which may induce long lasting remissions for MRD-negative patients randomized to stopping treatment after 15 induction cycles.

Key Dates

Start date

Jun 23, 2017

Status verified

Aug 2022

Primary completion

Jun 30, 2021

Completion

Jun 21, 2026

Study Design

Enrollment

230 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Experimental: Ibrutinib until progression/relapse
  All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles. MRDpositive patients (PB and BM) will continue on Ibrutinib maintenance (non-randomized group) until progression/relapse
• Experimental: Arm A
  All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles. MRD negative patients (PB and BM) will be randomized to Arm A or Arm B. Arm A: Ibrutinib until progression/relapse (Continuous ibrutinib treatment until toxicity or progression)
• Experimental: Arm B
  All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles. MRD negative patients (PB and BM) will be randomized to Arm A or Arm B. Arm B: Observation until event. Patients randomized to Arm B will get reinitiation of therapy during the observation period in case of: * progression according to IWCLL criteria or * MRD≥10-3 (PB) and at least one month later MRD ≥10-2 (PB). Treatment reinitiation will consist of ibrutinib and venetoclax (with ramp up of venetoclax from cycle 1) for 12 cycles

Primary Outcome Measure

Number of patients with progression free survival 27 months after starting treatment [ Time Frame: 27 months after last patient in trial ]