RecruitingPhase 2NCT02115295

Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia

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

Sponsor

M.D. Anderson Cancer Center

Enrollment

508 participants

Start Date

May 19, 2014

Study Type

INTERVENTIONAL

Conditions

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

Summary

This phase II trial studies how well cladribine, idarubicin, cytarabine, and venetoclax work in patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. Drugs used in chemotherapy, such as cladribine, idarubicin, cytarabine, and venetoclax, 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.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria11

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.
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.
For Salvage cohort: Patients with previously treated, relapsed or refractory AML, Acute Biphenotypic Leukemia, or CML in Myeloid Blast Phase are eligible.
Age \</= 65 years.
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
ECOG performance status of ≤ 2.
A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
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 Criteria4

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.
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.
Patient with documented hypersensitivity to any of the components of the chemotherapy program.
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.