Clinical Trial: Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory AML and MDS

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase II Trial Examining Epigenetic Priming With Decitabine Followed by Idarubicin and Cytarabine for Patients With Relapsed or Refractory AML.

Brief Summary: The goals of this study are to learn about the effectiveness, the side-effects, if waiting to give the idarubicin and cytarabine may change the side effects or effectiveness, and to identify factors to predict for responses to this therapy. The trial will examine combination of three chemotherapy drugs. These drugs are decitabine, idarubicin, and cytarabine.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the morphologic complete remission (CR) rates using a decitabine (DAC)-priming followed by idarubicin (IDA) and cytarabine (ARAC) in patients with relapsed or refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To determine CR without minimal residual disease (CRMRD-), CR with incomplete blood count recovery (CRi), CR with minimal residual disease (CRMRD+), and CR with incomplete blood count recovery and with minimal residual disease (CRiMRD+) rates.

II. To estimate the frequency and severity of regimen-related toxicities.

III. To identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and expression changes including interferon regulatory factor [IRF]8) associated with clinical responses.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive decitabine intravenously (IV) over 1 hour on days -4 to 0, cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 10-15 minutes on days 1-3.

ARM II: Patients receive decitabine IV over 1 hour on days -9 to -5 and cytarabine and idarubicin as in Arm I.

In both arms, treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 5 years.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Number of Participants Who Achieved Morphologic CR [ Time Frame: Participants were monitored up until the point when they went off study following completion of the treatment (3 months) ]

Morphologic complete remission (CR): Absolute Neutrophil Count (ANC)≥1,000/uL, platelet count ≥100,000/uL, <5% Bone Marrow (BM) blasts, no Auer rods (cytoplasmic inclusions which result from an abnormal fusion of the primary (azurophilic) granules), no morphologic dysplasia, and no evidence of extramedullary disease


Original Primary Outcome: Morphologic CR rates defined as absolute neutrophil count (ANC) at least 1,000/μL, platelet count at least 100,000/μL, less than 5% BM blasts, no Auer rods, no morphologic dysplasia, and no evidence of extramedullary disease [ Time Frame: Assessed for up to 5 years ]

The trial will follow an optimal two-stage Simon design. This design has an overall type 1 error rate (alpha) of 10%, and a power of 82% for a true CR rate of 30%. The probability of stopping after the first stage is 70%, if the true CR rate is 10%, and 11%, if the true CR rate is 30%.


Current Secondary Outcome:

  • Resistant Disease Defined as Patient Survives at Least 14 Days After Completion of the Last Dose of Induction or Re-induction But Has Persistent Leukemia in Peripheral Blood (PB) or BM [ Time Frame: Assessed for up to 90 days ]
  • Cytogenetic Response Defined as no Detectable Cytogenetic Abnormality in a Subsequent BM Specimen After Induction or Re-induction [ Time Frame: Assessed for up to 5 years ]
  • CRMRD- Defined as Morphologic CR Without Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • CRi Defined as Meeting All Criteria for a Morphologic CR But ANC Remains Less Than 1,000/μL and/or Platelet Count Less Than 100,000/μL [ Time Frame: Assessed for up to 5 years ]
  • CRMRD+ Defined as a Morphologic CR But With Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • CRiMRD+ Defined as Meeting All Criteria for a CRi But With Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • TRM With Each Course of Decitabine-priming, Idarubicin, and Cytarabine [ Time Frame: Assessed for up to Day 30 ]
  • Frequency and Severity of Grade 3, 4, and 5 Toxicities With Each Course of Decitabine-priming, Idarubicin, and Cytarabine According to NCI Common Terminology Criteria for Adverse Events Version (CTCAE) 4.0 [ Time Frame: Assessed for up to 3 months after completion study treatment ]
  • Severe Prolonged Aplasia [ Time Frame: Assessed for up to 45 days ]
  • Duration of Severe Neutropenia Defined as an ANC Less Than 500 [ Time Frame: Assessed for up to 5 years ]
  • Duration of Moderate Neutropenia Defined as an ANC Less Than 1000 [ Time Frame: Assessed for up to 5 years ]
  • Duration of Thrombocytopenia Defined as Platelet Count Less Than 100,000 [ Time Frame: Assessed for up to 5 years ]


Original Secondary Outcome:

  • Resistant Disease Defined as Patient Survives at Least 14 Days After Completion of the Last Dose of Induction or Re-induction But Has Persistent Leukemia in Peripheral Blood (PB) or BM [ Time Frame: 14 days ]
  • Cytogenetic Response Defined as no Detectable Cytogenetic Abnormality in a Subsequent BM Specimen After Induction or Re-induction [ Time Frame: 10 Days ]
  • CRMRD- Defined as Morphologic CR Without Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • CRi Defined as Meeting All Criteria for a Morphologic CR But ANC Remains Less Than 1,000/μL and/or Platelet Count Less Than 100,000/μL [ Time Frame: Assessed for up to 5 years ]
  • CRMRD+ Defined as a Morphologic CR But With Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • CRiMRD+ Defined as Meeting All Criteria for a CRi But With Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers [ Time Frame: Assessed for up to 5 years ]
  • TRM With Each Course of Decitabine-priming, Idarubicin, and Cytarabine [ Time Frame: Day 30 ]
  • Frequency and Severity of Grade 3, 4, and 5 Toxicities With Each Course of Decitabine-priming, Idarubicin, and Cytarabine According to NCI Common Terminology Criteria for Adverse Events Version (CTCAE) 4.0 [ Time Frame: 3 months after completion study treatment ]
  • Severe Prolonged Aplasia [ Time Frame: Up to 5 years ]
  • Duration of Severe Neutropenia Defined as an ANC Less Than 500 [ Time Frame: Up to 5 years ]
  • Duration of Moderate Neutropenia Defined as an ANC Less Than 1000 [ Time Frame: Up to 5 years ]
  • Duration of Thrombocytopenia Defined as Platelet Count Less Than 100,000 [ Time Frame: Up to 5 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: May 25, 2012
Date Started: July 2012
Date Completion:
Last Updated: February 14, 2017
Last Verified: February 2017