Evaluation of Risk-Adapted and MRD-Driven Strategy for Untreated Fit Patients With Intermediate Risk Chronic Lymphocytic Leukemia

Conditions

• Fit Patients
• Intermediate Risk Chronic Lymphocytic Leukemia
• Risk-Adapted and MRD-Driven Strategy

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• venetoclax and ibrutinib (I+VEN) — DRUG
  The treatment will start with ibrutinib alone for 3 months (lead-in phase) from Month 1 to Month 3 and then venetoclax will be added from Month 4 with an initial ramp-up period. The total duration of treatment with (I+VEN) will depend on the response achieved at Month 9: * if BM MRD at M9 \< 0.01%, the treatment with (I+VEN) will be continued for 6 additional months until Month 15 and stopped then. MRD will be assessed at Month 15 (PB), Month 21 (PB) and Month 27 (PB and BM) * if BM MRD at M9 ≥ 0.01%, the treatment with (I+VEN) will be continued for 18 additional months until Month 27 and stopped then, whatever the results of MRD assessments that will be performed at the same time points as above.
• FCR — DRUG
  All patients will receive 6 cycles of FCR administered at 4 weeks intervals (D1 = D29) from Month 1 to Month 6. 6 cycles of FCR will be administered at 4 weeks intervals (D1 = D29) from Month 1 to Month 6.

Study Details

The aim of this study is to test the potential benefit of an innovative combination of targeted therapy over the standard the immunochemotherapy (FCR). The interest in this study resides in an MRD driven discontinuation of the novel agents, and a fixed maximum duration of these agents. This design allows a true comparison of the efficacy of IV with the immuno-chemotherapy at 2 years of treatment and later. Finally, other trials propose to include to all risk categories of patients, and we are developing here a stratification preventing the dilution of the results. The intermediate risk patients are the ones for which alternative to chemotherapy is critical, as chemotherapy is likely to alter the clonal evolution of their disease, whereas the low risk patients are already doing well with standard treatment and are likely to benefit from other therapies as well. The high risk patients, id est patients with 17p deletion and or TP 53 mutational status responded very well to new drugs as BTK inhibitors or BLC2 inhibitors.

Key Dates

Start date

Sep 27, 2019

Status verified

Nov 2025

Primary completion

Apr 3, 2023

Completion

Jan 30, 2025

Study Design

Enrollment

120 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: FCR
  FCR : * rituximab (R): 375 mg/m² IV D1 cycle 1 and 500 mg/m² IV D1 cycles 2 to 6. * fludarabine (F): 40 mg/m² orally, D2 to D4 - cycles 1 to 6. * cyclophosphamide (C): 250 mg/m² orally, D2 to D4 - cycles 1 to 6.
• Experimental: venetoclax and ibrutinib (I+VEN)
  * ibrutinib: 420 mg/d orally, continuously from Month 1 to the end of treatment, either Month 15 or Month 27 * venetoclax: stepwise weekly dose ramp-up beginning at Month 4 from a starting dose of 20 mg/d to the final dose of 400 mg/d (20, 50, 100, 200 and then 400 mg) over a 5 weeks, and then 400 mg/d continuously from Month 5 to the end of treatment, either Month 15 or Month 27.

Primary Outcome Measure

Minimal residual disease (MRD) in bone marrow (BM) < 0.01% at month 27 [ Time Frame: 27 month after beginning FCR or venetoclax + ibrutinib ]