Cladribine, Cytarabine, and Decitabine With or Without Venetoclax and Gilteritinib in Treating Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
This phase II trial studies how well cladribine, cytarabine, and decitabine with or without venetoclax and gilteritinib work in treating patients with untreated acute myeloid leukemia, acute myeloid leukemia that has come back after a period of improvement (relapsed), acute myeloid leukemia that does not respond to treatment (refractory) or patients with high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as cladribine, cytarabine, and decitabine, 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. 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. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cladribine, cytarabine, and decitabine with or without venetoclax and gilteritinib may work well in treating patients with untreated, relapsed, or refractory acute myeloid leukemia and patients with high-risk myelodysplastic syndrome.
Inclusion Criteria
- COHORT 1: Patients with previously untreated AML or high risk myelodysplastic syndrome (MDS) (>= 10 % blasts or International Prognostic Scoring System [IPSS] >= intermediate-2); prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, all-trans retinoic acid (ATRA), or total dose of cytarabine up to 2 g is allowed; patients with history of myelodysplastic syndrome (MDS) transformed to AML are eligible regardless of their prior therapy for MDS provided they have not received prior therapy for for AML
- COHORT 1: Age >= 60 years. Patients aged < 60 years who are unsuitable for standard induction therapy may be eligible after discussion with principal investigator (PI)
- COHORT 1: Bilirubin =< 2 mg/dL
- COHORT 1: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
- COHORT 1: Creatinine =< 1.5 x ULN
- COHORT 1: Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- COHORT 1: A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
- COHORT 1: 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
- COHORT 1: Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine
- COHORT 2: Patients with previously untreated AML who are not currently eligible for other frontline clinical trials of AML therapy; prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2 g is allowed; patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML
- COHORT 2: Age >= 18 years who are unsuitable for standard induction therapy are eligible after discussion with PI
- COHORT 2: Creatinine >= 2 mg/dL
- COHORT 2: Total bilirubin >= 2 mg/dL
- COHORT 2: ECOG performance status equal to 3 or 4
- COHORT 2: Is ineligible for participation in a protocol of higher priority
- COHORT 2: A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
- COHORT 2: 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
- COHORT 2: Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine
- COHORT 3: Patients with relapsed and or refractory AML who have received at least one prior therapy for their AML
- COHORT 3: Age >= 18 years
- COHORT 3: Bilirubin =< 2mg/dL
- COHORT 3: AST and/or ALT =< 3 x ULN
- COHORT 3: creatinine =< 1.5 x ULN
- COHORT 3: ECOG performance status of ≤ 2
- COHORT 3: A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
- COHORT 3: 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
- COHORT 3: Prior therapy with venetoclax will be allowed
Exclusion Criteria
- COHORT 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
- COHORT 1: Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- COHORT 1: Patient with documented hypersensitivity to any of the components of the chemotherapy program
- COHORT 1: 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
- COHORT 2: 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
- COHORT 2: Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, unless these illness are judged to be related to the underlying leukemia
- COHORT 2: Patient with documented hypersensitivity to any of the components of the chemotherapy program
- COHORT 2: 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
- COHORT 3: 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
- COHORT 3: Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- COHRT 3: Patient with documented hypersensitivity to any of the components of the chemotherapy program
- COHORT 3: 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
Additional locations may be listed on ClinicalTrials.gov for NCT01515527.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVES:
I. To assess disease-free survival (DFS) of patients with acute myeloid leukemia (AML) treated with cladribine plus low-dose cytarabine (LDAC) alternating with decitabine. (Frontline cohort; Cohort 1)
II. To assess survival at 60 days from initiation of therapy on protocol. (Frontline cohort ineligible for trials; Cohort 2)
III. To assess the overall response rate (complete remission [CR]/CR with incomplete count recovery [CRi]/marrow leukemia free status [MLFS]) of cladribine plus LDAC combined with venetoclax and gilteritinib in patients with relapsed and/or refractory (R/R) AML. (Salvage cohort; Cohort 3)
SECONDARY OBJECTIVES:
I. To assess overall survival (OS) of patients with AML treated with the backbone of cladribine plus LDAC alternating with decitabine in frontline and R/R AML.
II. To assess the complete remission (CR) rate of patients with AML treated with the backbone of cladribine plus LDAC alternating with decitabine in frontline and R/R AML.
III. To assess the overall response rate of patients with AML treated with the backbone of cladribine plus LDAC alternating with decitabine in frontline and R/R AML.
IV. To assess toxicity and induction mortality of patients with AML treated with the backbone of cladribine plus LDAC alternating with decitabine in frontline and R/R AML.
V. To assess the 30-day OS rate and disease-free survival (DFS) (for frontline cohort ineligible for trials).
VI. To assess the frequency of patients in the R/R setting that are able to proceed with allogeneic SCT (overall and among responding patients).
OUTLINE: Patients with untreated AML and myelodysplastic syndrome are assigned to cohorts 1 and 2. Patients with relapsed or refractory AML are assigned to cohort 3.
COHORTS 1 and 2:
INDUCTION THERAPY: Patients receive cladribine intravenously (IV) over 1-2 hours on days 1-5 of each cycle and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 of each cycle. Cycles may repeat every 28 days for 1 or 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients receive cladribine IV over 1-2 hours on days 1-3 of each cycle and cytarabine SC BID on days 1-10 of each cycle alternating with decitabine IV over 1-2 hours on days 1-5 of each cycle. Cycles repeats every 28 days for 16 or 17 cycles (no more than 18 cycles total between induction and consolidation) in the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
COHORT 3:
INDUCTION THERAPY: Patients receive cladarbine IV, over 1-2 hours on days 1-5, cytarbine SC BID on days 1-10, venetoclax orally (PO) once daily (QD) on days 1-10 and gilteritinib PO QD on days 1-14 of each cycle. Cycles may repeat every 28 days for 1 or 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients receive cladarbine IV, over 1-2 hours on days 1-3, cytarbine SC BID on days 1-7, venetoclax PO QD on days 1-7 and gilteritinib PO QD on days 1-14 of each cycle. Cycles repeat every 28 days for 1 or 2 cycles (no more than 3 cycles total between induction and consolidation) in the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 6 -12 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorTapan M. Kadia
- Primary ID2011-0987
- Secondary IDsNCI-2012-00145
- ClinicalTrials.gov IDNCT01515527