NCT04968015

Venetoclax + Cytarabine Versus Idarubicin + Cytarabine : Efficacity Assessment as Post-remission Therapy to Elderly Patients With Acute Myeloid Leukemia in First Remission

A Phase II Randomized Study to Assess the Efficacy on Outcome of Venetoclax Combined With Cytarabine Versus Idarubicin Combined With Cytarabine Administered as Post-remission Therapy to Elderly Patients With Acute Myeloid Leukemia in First Remission

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 134 (estimated)
• Sponsor: French Innovative Leukemia Organisation · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

For the FILO group, the standard of care for induction chemotherapy of elderly fit patients with AML is represented by the combination of Cytarabine, Idarubicin and Lomustine. The superiority of this combination was confirmed in a larger prospective study the LAMSA-2007. This induction treatment, followed by six courses of consolidation (Idarubicin and Cytarabine) followed then by a period of 6-month maintenance therapy, allows up to 80 % of remission, and a RFS of 46 % at 2 years. The aim of the study is to assess the efficacy on outcome of Venetoclax combined with Cytarabine versus Idarubicin combined with Cytarabine administered as post-remission therapy to elderly patients with acute myeloid leukemia in first complete remission (CR) following induction chemotherapy.

Detailed description

Acute myeloid leukemia is characterized by the clonal expansion of myeloid blasts in the bone marrow, peripheral blood and extramedullary tissues which disrupts normal hematopoiesis. It is the most common form of acute leukemia in adults with an estimated 19,950 new cases and 10,430 deaths in 2016 in the United States. The prevalence is approximately 36,000 in the US alone. The median age of diagnosis is 67 years, with 55 % of the patients diagnosed at 65 years or older, and approximately a third of them are diagnosed over the age of 75. Due to a higher frequency of poor prognosis factors such as adverse cytogenetics, previous history of myelodysplastic syndrome (MDS) or therapy-related AML (t-AML), the prognosis of elderly AML remains dismal in patients \> 60 years. The complete remission rate achieved after induction chemotherapy is lower than in young adults, and the remission duration is seldom longer than a year. Consequently, the overall survival of these patients rarely excesses 10-15 % beyond 5 years from diagnosis. For this group of patients, improving the efficacy of post induction chemotherapy and preventing relapse, without increasing the treatment-related mortality, remain a challenge. For the FILO group, the standard of care for induction chemotherapy of elderly fit patients with AML is represented by the combination of Cytarabine, Idarubicin and Lomustine (ICL: Idarubicin 8 mg per square meter per day, IV on days 1-5, Cytarabine 100 mg per square meter per day on days 1-7 IV continuously, Lomustine 200 mg per square meter orally at day 1). This induction treatment, followed by six courses of consolidation, consisting of reduced doses of Idarubicin 8 mg per square meter per day IV on day 1 and Cytarabine 50 mg per square meter/12h/d subcutaneously on days 1-5 followed then by a period of 6-month maintenance therapy, allows up to 80 % of remission, an improvement in 2-year Event Free Survival from 26 % to 41 %, and a 2 year relapse free survival improvement from of 33 % to 46 % for patients without unfavorable cytogenetics. Venetoclax is a potent, selective and orally bioavailable small molecule inhibitor of BCL-2 (B-cell lymphoma 2), an anti-apoptotic protein which overexpression is associated with tumor initiation, disease progression, and drug resistance, and is thus a compelling target for anti-tumor therapy. Phse I/II studies have assessed venetoclax as single agent or in combination with low dose Cytarabine (LDAC) in upfront treatment of AML patients aged ≥ 65 years old and not eligible for standard Cytarabine and anthracycline-based induction therapy with encouraging results. The aim of the study is to assess the efficacy on outcome of Venetoclax combined with Cytarabine versus Idarubicin combined with Cytarabine administered as post-remission therapy to elderly patients with acute myeloid leukemia in first complete remission (CR) following induction chemotherapy. Subjects will be randomized 1:1 to receive Venetoclax or Idarubicin associated to Cytarabine for 6 cycles x 28 days. Patients will be followed until progression or death or until the end of study defined by the number of relapse-free survival (RFS) events and last patient treatment period.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine-Venetoclax Association	Consolidation treatment with cytarabine + venetoclax
DRUG	Cytarabine-Idarubicin Association	Consolidation treatment with cytarabine + idarubicin

Timeline

• Start date: 2022-05-25
• Primary completion: 2025-08-15
• Completion: 2029-01-31
• First posted: 2021-07-20
• Last updated: 2024-06-27

Locations

26 sites across 1 country: France