Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML
NCT Number: NCT06504459
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Acute Monocytic Leukemia|Acute Myeloid Leukemia
Interventions: DRUG: Azacitidine|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|DRUG: Cladribine|DRUG: Cytarabine|PROCEDURE: Echocardiography|PROCEDURE: Lumbar Puncture|PROCEDURE: Multigated Acquisition Scan|OTHER: Questionnaire Administration|DRUG: Venetoclax
Sponsor: OHSU Knight Cancer Institute
Collaborators: Oregon Health and Science University|AbbVie
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-31
Completion Date: 2028-05-01
Locations: OHSU Knight Cancer Institute, Portland, Oregon, 97239, United States

Summary:
This phase II trial tests how well venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax works in treating patients with newly diagnosed monocytic acute myeloid leukemia (AML) and active signaling mutated AML. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as cladribine, cytarabine and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed monocytic AML and active signaling mutated AML.

Primary Outcome Measures: Composite complete remission (CRc) rate, CRc is defined as achievement of complete remission (CR), CR with partial hematologic recovery (CRh) or CR with incomplete blood count recovery (CRi) after induction (or re-induction). The CRc rate will be computed on the safety set and presented with a point-estimate and exact binomial 95% confidence interval (CI). CRc will also be modeled with univariable logistic regressions, applied to the efficacy set, to determine if any baseline patient or disease feature is correlated with clinical response., At start of treatment to post-induction disease assessment (Cycle 1 Day 21 or Cycle 2 Day 21. Each cycle is 28 days)
Secondary Outcome Measures: Overall response rate (ORR), ORR will be defined as the proportion of evaluable participants who attain a partial remission (PR) or better (i.e., CR, CRh, CRi, morphologic leukemia-free state \[MLFS\], or PR) while on investigational treatment. ORR will be computed for both the safety set and the efficacy set and presented with a point estimate and exact binomial CI. ORR will also be modeled with univariable logistic regressions with baseline patient and disease features as predictors and results considered hypothesis-generating., At start of treatment to post-induction disease assessment (Cycle 1 Day 21 or Cycle 2 Day 21. Each cycle is 28 days)|Overall survival (OS), OS will be computed for both the safety set and the efficacy set, and estimated with the Kaplan-Meier method. Median OS and OS rates at common landmark times (e.g., 1 year, 2 years) will be estimated with 95% log-log CIs. For both sets, univariable Cox models will be fit to OS to assess the impact of baseline patient and disease features with results (i.e., unadjusted hazard ratios and Wald test p-values) considered hypothesis-generating. Median follow-up will utilize a patient's OS measurement and censoring status and be estimated using the reverse Kaplan-Meier method., At start of treatment to death up to 2 years|Event-free survival (EFS), EFS will be measured from start of treatment to the earliest date of treatment failure, progressive disease, or death from any cause. EFS will be estimated for the efficacy set using the Kaplan-Meier method, with median EFS and EFS rates at common landmark times presented with 05% log-log CIs. EFS will be alternatively estimated upon assigning 1-day event times to participants who never achieve MLFS or better. Univariable Cox models will be fit to EFS to assess the impact of baseline patient and disease features with model results considered hypothesis-generating., At start of treatment to primary refractory disease, hematologic relapse, discontinuation of treatment due to toxicity, disease progression or death up to 2 years|Duration of response (DOR), DOR will be measured from the first date of documented hematologic response to the earliest of the following occurrences: hematologic relapse, disease progression (clinical or morphologic), or any-cause death. DOR will be estimated by the Kaplan-Meier method. Median DOR will be presented with a 95% log-log CI., At first date of documented ≥ MLFS or better to primary refractory disease, hematologic relapse, discontinuation of treatment due to toxicity, disease progression or death up to 2 years|Incidence of grade ≥ 3 adverse events (AEs), AEs severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0., At start of treatment up to 30 days after last dose of any study drug|Percentage of patients achieving 80% relative dose intensity, The percentage of participants achieving 80% relative dose intensity will be reported., At start of treatment to end of treatment up to 1 year and 5 months