Clinical Trials /

Cytarabine, Idarubicin, Liposome-encapsulated Daunorubicin-Cytarabine or Decitabine in Treating Older Patients With Acute Myeloid Leukemia

NCT03226418

Description:

This phase II trial studies how well cytarabine and idarubicin or decitabine work in treating patients with acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, idarubicin and liposome-encapsulated daunorubicin-cytarabine, 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. 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 or decitabine may work better in treating patients with acute myeloid leukemia based on clinicogenetic risk stratification.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cytarabine and Idarubicin or Decitabine in Treating Older Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
  • Official Title: A Phase II Study of the Impact of Clinicogenetic Risk-Stratified Management and Systemic Inflammation on Outcomes of Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome in Older Patients

Clinical Trial IDs

  • ORG STUDY ID: 179-17
  • SECONDARY ID: NCI-2017-01285
  • SECONDARY ID: 179-17
  • SECONDARY ID: P30CA036727
  • NCT ID: NCT03226418

Conditions

  • Adult Acute Myeloid Leukemia
  • Adult Myelodysplastic Syndrome
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Group I (lower-risk)
Decitabine5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineGroup II (higher-risk)
Idarubicin4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDRGroup I (lower-risk)

Purpose

This phase II trial studies how well cytarabine and idarubicin or decitabine work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as cytarabine and idarubicin, 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. Decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving patients cytarabine and idarubicin or decitabine may work better in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome based on clinicogenetic risk stratification.

Detailed Description

      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) or
      high-risk myelodysplastic syndrome (MDS), 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 with protocol specified lower-risk and higher-risk newly diagnosed AML or MDS.

      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 assess the impact of Glasgow prognostic score (marker of systemic inflammation) on
      the rate of complete remission and mortality at 90 days in older patients, who receive
      clinicogenetic risk-stratified therapy allocation.

      IV. To evaluate the influence of baseline functional status on the quality of life and
      neurocognitive status at baseline and at 90 days in older patients.

      V. To evaluate the influence of Glasgow prognostic score on the quality of life and
      neurocognitive status at baseline and at 90 days in older patients.

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

      TERTIARY 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 and high-risk MDS 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.

      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) over 1-3 hours on
      days 1-7 and idarubicin over 10-15 minutes on days 1-3. Treatment repeats for 4 weeks for 1
      course 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
      courses in the absence of disease progression or unacceptable toxicity.

      GROUP II:

      LOW-INTENSITY INDUCTION: Patients receive decitabine IV over 1-3 hours on days 1-10.
      Treatment repeats every 4 weeks for 1-4 courses in the absence of disease progression or
      unacceptable toxicity.

      LOW-INTENSITY CONSOLIDATION: Patients who achieve complete remission, receive decitabine IV
      over 1-3 hours on days 1-5. Treatment repeats every 4 weeks for 6 or more courses in the
      absence of disease progression or unacceptable toxicity.

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

Trial Arms

NameTypeDescriptionInterventions
Group I (lower-risk)ExperimentalINTENSIVE INDUCTION THERAPY: Patients receive cytarabine IV over 1-3 hours on days 1-7 and idarubicin over 10-15 minutes on days 1-3. Treatment repeats for 4 weeks for 1 course in the absence of disease progression or unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours BID on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity.
  • Cytarabine
  • Idarubicin
Group II (higher-risk)ExperimentalLOW-INTENSITY INDUCTION: Patients receive decitabine IV over 1-3 hours on days 1-10. Treatment repeats every 4 weeks for 1-4 courses in the absence of disease progression or unacceptable toxicity. LOW-INTENSITY CONSOLIDATION: Patients who receive complete remission, receive decitabine IV over 1-3 hours on days 1-5. Treatment repeats every 4 weeks for 6 or more courses in the absence of disease progression or unacceptable toxicity.
  • Decitabine

Eligibility Criteria

        Inclusion Criteria:

          -  A new diagnosis of de novo, secondary or treatment-related AML; or MDS with high- or
             very high-risk disease based on revised international prognostic scoring system

        Exclusion Criteria:

          -  Acute promyelocytic leukemia

          -  Relapsed or refractory AML, who require salvage therapy

          -  Secondary AML in patients, who have been exposed to decitabine or azacitidine
             previously for antecedent hematologic disorders

          -  Patients, who require urgent initiation of chemotherapy (other than hydroxyurea) due
             to leukemia-related emergencies such as leukostasis, or disseminated intravascular
             coagulopathy; patients will not be excluded solely based on prior use of hydroxyurea;
             leukapheresis will be allowed

          -  Uncontrolled serious infection

          -  Uncontrolled arrhythmia, myocardial ischemia or congestive heart failure within the
             past 2 weeks that may constitute a contraindication for initiation of chemotherapy

          -  Ejection fraction < 45% will be an exclusion criteria for intensive chemotherapy

          -  Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< 45 ml/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;
             patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded

          -  Any other condition that may not allow safe use of chemotherapy based on the clinical
             judgment of the treating oncologist
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of complete remission and mortality in entire cohort
Time Frame:At 90 days
Safety Issue:
Description:Will be compared to the rate of complete remission and mortality in the historical control. A two-group comparison design (prospective cohort and historical control) will be used to explore the difference in 90-day mortality. The 90-day mortality will be compared between groups using a Pearson chi-square test. The trend in complete remission across Glasgow Prognostic Scores will be explored using the Cochran-Armitage Test for linear trend in proportions. The trend in 90-day mortality across Glasgow Prognostic will be explored using the Cochran-Armitage Test for linear trend in proportions. The

Secondary Outcome Measures

Measure:Baseline functional status
Time Frame:Up to 90 days
Safety Issue:
Description:Will evaluate the influence of baseline functional status on the quality of life and neurocognitive status. The association between categories of functional status and quality of life will be explored using analysis of variance (ANOVA); if assumptions of ANOVA fail, Kruskal Wallis will be used. The association between functional status (fit or vulnerable) and neurocognitive status (< 25 or 26 or higher) will be explored using a chi-square test.
Measure:Baseline functional status measure by geriatric assessment
Time Frame:At 90 days
Safety Issue:
Description:Will assess the impact of baseline functional status on the rate of complete remission and mortality.
Measure:Glasgow prognostic score
Time Frame:At 90 days
Safety Issue:
Description:Will assess the impact of Glasgow prognostic score (marker of systemic inflammation) on the rate of complete remission and mortality.
Measure:Glasgow prognostic score
Time Frame:Up to 90 days
Safety Issue:
Description:Will evaluate the influence of Glasgow prognostic score on the quality of life and neurocognitive status. The association between Glasgow Prognostic Score and quality of life will be explored using ANOVA; if assumptions of ANOVA fail, Kruskal Wallis will be used. The association between Glasgow Prognostic Score and neurocognitive status will be explored using a proportional odds model or cumulative logistic model, as appropriate.
Measure:Rate of complete remission and mortality in subsets
Time Frame:At 90 days
Safety Issue:
Description:Will be compared to the outcomes in the historical control. A two-group comparison design (prospective cohort and historical control) will be used to explore the difference in 90-day mortality. The 90-day mortality will be compared between groups using a Pearson chi-square test. The trend in complete remission across Glasgow Prognostic Scores will be explored using the Cochran-Armitage Test for linear trend in proportions. The trend in 90-day mortality across Glasgow Prognostic will be explored using the Cochran-Armitage Test for linear trend in proportions. The association between functional
Measure:Symptom burden
Time Frame:Up to 90 days following initiation of chemotherapy
Safety Issue:
Description:Will determine the symptom burden at diagnosis and 10, 30 and 90 days following initiation of chemotherapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Nebraska

Last Updated

July 20, 2017