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Cytarabine, Idarubicin and Liposome-encapsulated Daunorubicin-Cytarabine, or Venetoclax, Azacitidine, and Decitabine in Treating Older Patients with Acute Myeloid Leukemia

Trial Status: Active

This phase II trial studies how well cytarabine and idarubicin or venetoclax, azacitidine and decitabine work in treating patients with acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, idarubicin, liposome-encapsulated daunorubicin-cytarabine and venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving patients cytarabine, idarubicin, liposome-encapsulated daunorubicin-cytarabine, venetoclax, azacitidine or decitabine may work better in treating patients with acute myeloid leukemia based on clinicogenetic risk stratification.

Inclusion Criteria

  • A new diagnosis of de novo, secondary or treatment-related AML, other AML equivalent such as myeloid sarcoma, myelodysplastic syndrome in transformation to AML, or high-grade treatment-related myeloid neoplasm
  • Karnofsky Performance Status >= 60%
  • Subjects must be able and willingly give signed informed consent

Exclusion Criteria

  • Acute promyelocytic leukemia (APL); patients with brief exposure to all-trans retinoic acid (ATRA), arsenic trioxide (ATO) or similar product for suspected APL, who later turn out not to have APL, are eligible for the study
  • Relapsed or refractory AML, who require salvage therapy
  • Prior exposure to decitabine or azacitidine will be an exclusion criterion for the use of decitabine or azacitidine alone
  • Patients, who require urgent initiation of chemotherapy (other than debulking agent such as hydroxyurea or cyclophosphamide) due to leukemia-related emergencies such as leukostasis, or disseminated intravascular coagulopathy; patients will not be excluded solely based on prior use of debulking agent; prior or current use of leukapheresis will be allowed
  • Uncontrolled serious infection at the time of enrollment; infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, patients do not have signs of infection progression; progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection; persisting fever without other signs or symptoms will not be interpreted as progressing infection
  • Uncontrolled clinically significant arrhythmia, myocardial ischemia or congestive heart failure within the past 2 weeks, that is considered by the treating physician as a contraindication for initiation of chemotherapy; discussion with the principal investigator is encouraged if further clarification is required
  • Ejection fraction < 45% will be an exclusion criteria for intensive chemotherapy; such patients may receive low intensity therapy
  • Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< 45ml/minute or creatinine of >= 2 mg/dl) or liver dysfunction (e.g. aspartate aminotransferase [AST]/alanine aminotransferase (ALT) and/or bilirubin >= 2 times upper limit of normal [ULN]) at the time of enrollment that may prevent from safely using chemotherapy; such patients may be allowed to receive low-intensity chemotherapy; patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded; discussion with the principal investigator is encouraged if further clarification is required
  • Any other condition that may not allow safe use of chemotherapy based on the clinical judgment of the treating oncologist

Nebraska

Omaha
University of Nebraska Medical Center
Status: ACTIVE
Contact: Vijaya Raj Bhatt
Phone: 402-559-8008

PRIMARY OBJECTIVES:

I. To determine the rate of complete remission and mortality at 90 days in the entire cohort of older patients (>= 60 years) with newly diagnosed acute myeloid leukemia (AML) who receive clinicogenetic risk-stratified therapy allocation.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission and mortality at 90 days in subsets of older patients who receive intensive and low-intensity chemotherapy.

II. To assess the impact of baseline functional status (measured by geriatric assessment) on the rate of complete remission and mortality at 90 days in older patients, who receive clinicogenetic risk-stratified therapy allocation.

III. To evaluate the influence of baseline functional status on the quality of life, grades 3 and 4 toxicities (Common Terminology Criteria for Adverse Events [CTCAE] version 4.03 grades) and neurocognitive status at baseline and at 90 days in older patients.

IV. To determine the symptom burden at diagnosis and 10, 30 and 90 days following initiation of chemotherapy.

V. To determine proportion of patients with impairments detected by geriatric assessment.

EXPLORATORY OBJECTIVES:

I. To determine the percentage of older patients who receive allogeneic stem cell transplant during the study period.

II. To evaluate median time from diagnosis to complete remission and median time from diagnosis to receipt of transplant in the study population.

III. To determine the duration of remission, and overall survival at 1 and 2 years in the study population.

IV. To assess the predictive value of cytogenetic risk categories, FLT3 ITD, TP53 and other mutations in older patients treated with intensive and low intensity therapy.

V. To calculate the rate of response to salvage therapy among patients who have initially received low-intensity and intensive therapy.

VI. To evaluate the cause of deaths in older patients with AML who have received low-intensity and intensive therapy.

VII. To determine any correlation between time from diagnosis to initiation of therapy and mortality at 90 days in the study population.

VIII. To calculate the median time to peripheral blood blast clearance and its correlation to mortality at 90 days in the study population.

IX. To determine the percentage of older patients who achieve minimal residual disease negative status after intensive and low intensity therapy.

X. To measure length of stay for initial diagnosis and chemotherapy, and rehospitalization rate in older patients treated with intensive and low intensity therapy during the study period.

CORRELATIVE OBJECTIVES:

I. Quantify the association between levels of inflammatory cytokines and objectively measured physical function and cognition, quality of life and survival.

II. Determine whether expression levels of inflammatory cytokines are regulated by micro ribonucleic acids (miRNAs) in patients with AML.

OUTLINE: Patients are assigned to 1 or 2 groups based on cytogenetic and geriatric assessment-based risk stratification.

GROUP I:

INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3, or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Treatment continues for 1 cycle in the absence of disease progression or unacceptable toxicity.

INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II:

LOW-INTENSITY INDUCTION AND CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes on days 1-7 or decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for 3 cycles or more in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax orally (PO) daily for 3 months or more in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Nebraska Medical Center

Principal Investigator
Vijaya Raj Bhatt

  • Primary ID 179-17
  • Secondary IDs NCI-2017-01285
  • Clinicaltrials.gov ID NCT03226418