Combining cladribine, idarubicin, cytarabine, and venetoclax for treating certain blood cancers

Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With AML, HR MDS, or Myeloid Blast Phase of CML

This study is testing a new combination of four medications to see if it helps people with certain types of blood cancers feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 508 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Drugs / interventions: chemotherapy, gilteritinib
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT02115295 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of a combination of cladribine, idarubicin, cytarabine, and venetoclax in patients diagnosed with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. The study aims to determine the complete response rate and overall response rate of this treatment regimen, as well as assess overall survival and event-free survival among participants. Additionally, it explores the safety and tolerability of the drug combination and investigates potential molecular biomarkers that could predict treatment response.

Who should consider this trial

Good fit: Ideal candidates include patients aged 65 years or younger with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia.

Not a fit: Patients with prior potentially-curative therapy for leukemia or those over 65 years old may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve response rates and survival outcomes for patients with aggressive blood cancers.

How similar studies have performed: Other studies have shown promising results with similar drug combinations in treating acute myeloid leukemia, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients with a diagnosis of AML, Acute Biphenotypic Leukemia, or high risk MDS (\>/= 10% blasts or IPSS \>/= intermediate-2) will be eligible. Patients with CML in Myeloid Blast Phase are also eligible.
2. For Frontline cohort (1 or 4): No prior potentially-curative therapy for leukemia. Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed. Patients deemed able to receive venetoclax (ie. insurance clearance) will be assigned to Frontline cohort 4. Patients with secondary AMLwho have been treated for their antecedent myeloid neoplasm will be enrolled into the separate Secondary AML cohort.
3. For Salvage cohort: Patients with previously treated, relapsed or refractory AML, Acute Biphenotypic Leukemia, or CML in Myeloid Blast Phase are eligible.
4. Age \</= 65 years.
5. Adequate organ function as defined below:

   * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN - or \<5 x ULN if related to leukemic involvement)
   * kidney function (creatinine \< 1.5 x ULN ).
   * known cardiac ejection fraction of \> or = 45% within the past 6 months
6. ECOG performance status of ≤ 2.
7. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
8. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.

Exclusion Criteria:

1. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
2. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patient with documented hypersensitivity to any of the components of the chemotherapy program.
4. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Tapan M Kadia — M.D. Anderson Cancer Center
• Study coordinator: Tapan Kadia

Conditions: Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Blasts 10 Percent or More of Peripheral Blood White Cells, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome