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

  • STATUS
    Recruiting
  • End date
    May 19, 2022
  • participants needed
    408
  • sponsor
    M.D. Anderson Cancer Center
Updated on 25 January 2021
cancer
chronic myeloid leukemia
myeloid leukemia
blast crisis
hydroxyurea
cytarabine
tretinoin
ejection fraction
secondary aml
decitabine
growth factor
leukemia
idarubicin
azacitidine
refractory acute myeloid leukemia (aml)
secondary acute myeloid leukemia
blast cells
cladribine
venetoclax
hematopoietic growth factors
midostaurin

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.

Description

PRIMARY OBJECTIVES:

I. To determine the complete response rate (CR) of cladribine in combination with idarubicin and cytarabine (araC) in patients with acute myeloid leukemia (AML), high risk (HR) myelodysplastic syndrome (MDS), or myeloid blast phase of chronic myeloid leukemia (CML).

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) of cladribine in combination with idarubicin and araC in patients with AML, HR MDS, or myeloid blast phase of CML.

II. To assess overall survival (OS) and event free survival (EFS) of patients treated with cladribine, idarubicin, and araC (cytarabine).

III. To assess the duration of response to the combination in patients with AML, HR MDS, or myeloid blast phase of CML.

IV. To determine the safety and tolerability of the combination in patients with AML, HR MDS, or myeloid blast phase of CML.

EXPLORATORY OBJECTIVES:

I. To study and describe the relationship between pretreatment patient/disease characteristics (including AML-associated molecular abnormalities) and outcome.

II. To identify molecular biomarkers predictive of response to therapy. III. To study and describe the relationship between patient/disease characteristics, use of intrathecal prophylaxis, and incidence of leptomeningeal disease.

OUTLINE

INDUCTION: Patients receive cladribine intravenously (IV) and cytarabine IV over 1-2 hours on days 1-5 and idarubicin IV over 30-60 minutes on days 1-3. Patients with untreated AML and MDS also receive venetoclax orally (PO) on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO twice daily (BID) on days 6-19 or gilteritinib PO once daily (QD) on days 1-14. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive cladribine IV and cytarabine IV over 1-2 hours on days 1-3 and idarubicin IV over 30-60 minutes on days 1-2. Patients with untreated AML and MDS also receive venetoclax PO on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO BID on days 6-19 or gilteritinib PO QD. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Details
Condition Blast Crisis, Bone marrow disorder, Bone marrow disorder, Preleukemia, leukemia, leukemia, Leukemia (Pediatric), Acute myeloid leukemia, Acute Myelogenous Leukemia (AML), Acute myeloid leukemia, Acute biphenotypic leukemia, MYELODYSPLASTIC SYNDROME, Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia, de Novo Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome, Refractory Acute Myeloid Leukemia, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Leukemia (Pediatric), Recurrent Acute Myeloid Leukemia, Blasts 10 Percent or More of Peripheral Blood White Cells, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive, myelodysplastic syndromes, myelodysplastic syndrome (mds), secondary aml, biphenotypic acute leukemia, acute myelogenous leukemia, anll, acute myeloblastic leukemia, refractory acute myeloid leukemia (aml), Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Treatment laboratory biomarker analysis, cytarabine, Idarubicin, cladribine, Phone Calls, Gilteritinib, venetoclax, Midostaurin
Clinical Study IdentifierNCT02115295
SponsorM.D. Anderson Cancer Center
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients with a diagnosis of AML, acute biphenotypic leukemia, or high risk MDS (>= 10% blasts or International Prognostic Scoring System [IPSS] >= intermediate-2) will be eligible; patients with CML in myeloid blast phase are also eligible
For frontline cohorts (1 or 4): no prior potentially curative therapy for leukemia; prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, tretinoin (ATRA), or a total dose of cytarabine up to 2 g (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 AML who 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
Bilirubin =< 2 mg/dL
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if related to leukemic involvement
Creatinine =<1.5 x ULN
Known cardiac ejection fraction of >= 45% within the past 6 months
Eastern Cooperative Oncology Group (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 or his legally authorized representative is required prior to their enrollment on the protocol

Exclusion Criteria

Pregnant women are excluded from this study; breastfeeding should also be avoided
Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [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
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