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Decitabine and Cytarabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, or Myeloproliferative Neoplasm

NCT02121418

Description:

This clinical trial studies decitabine and cytarabine in treating older patients with newly diagnosed acute myeloid leukemia, myelodysplastic syndrome that is likely to come back or spread to other places in the body, or myeloproliferative neoplasm. Drugs used in chemotherapy, such as decitabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine and cytarabine may work better than standard therapies in treating cancers of the bone marrow and blood cells, such as acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Decitabine and Cytarabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, or Myeloproliferative Neoplasm
  • Official Title: Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: 9019
  • SECONDARY ID: NCI-2014-00769
  • SECONDARY ID: 9019
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT02121418

Conditions

  • Chronic Myelomonocytic Leukemia-2
  • Myelodysplastic Syndrome
  • Myeloproliferative Neoplasm
  • Untreated Adult 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-28453Treatment (decitabine, cytarabine)
Decitabine5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineTreatment (decitabine, cytarabine)

Purpose

This clinical trial studies decitabine and cytarabine in treating older patients with newly diagnosed acute myeloid leukemia, myelodysplastic syndrome that is likely to come back or spread to other places in the body, or myeloproliferative neoplasm. Drugs used in chemotherapy, such as decitabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine and cytarabine may work better than standard therapies in treating cancers of the bone marrow and blood cells, such as acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Examine whether a combination of decitabine given for 10 days (days 1-10), rather than the
      usual 5 days, plus "standard dose cytarabine (ara-C) (100 mg/m^2 daily days 1-7) might
      improve 6-month survival probability from the historical 65% to 80% in patients age >= 60
      with newly diagnosed acute myeloid leukemia (AML).

      II. Test whether this combination might maintain complete response (CR) rate at our historic
      45% in these patients.

      III. Study factors that lead physicians to escalate or maintain ara-C doses in those patients
      who have had an "intermediate response" short of CR to the first 2 cycles of the combination.

      IV. While maintaining awareness of confounding covariates, examine the effect of such dose
      escalation on CR rate.

      OUTLINE:

      Patients receive decitabine intravenously (IV) daily on days 1-10 and cytarabine IV once
      daily (QD) on days 1-7. Treatment repeats every 28-35 days for 2 courses in the absence of
      disease progression or unacceptable toxicity. After course 3, patients achieving remission
      will receive 1-2 more courses of therapy at the same dose. Patients in remission with
      significant side effects will receive decitabine and cytarabine at decreased doses. Patients
      not achieving remission will not receive any more treatment.

      After completion of study treatment, patients are followed up for 6 months and then
      periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (decitabine, cytarabine)ExperimentalPatients receive decitabine IV daily on days 1-10 and cytarabine IV QD on days 1-7. Treatment repeats every 28-35 days for 2 courses in the absence of disease progression or unacceptable toxicity. After course 3, patients achieving remission will receive 1-2 more courses of therapy at the same dose. Patients in remission with significant side effects will receive decitabine and cytarabine at decreased doses. Patients not achieving remission will not receive any more treatment.
  • Cytarabine
  • Decitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Newly-diagnosed AML by World Health Organization (WHO) criteria (>= 20% myeloid blasts
             by morphology in either blood or marrow)

          -  High-risk myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN)
             including chronic myelomonocytic leukemia 2 (CMML2) as defined by 10-19% myeloid
             blasts in either blood or marrow

          -  Patients may have received azacitidine, decitabine, or lenalidomide but no "cytotoxic
             therapy" such as ara-C or anthracyclines; data suggest that failure to respond to
             azacitidine reduces probability of response to 3+7; hence in the interest of having a
             relatively homogeneous population, while patients who have received and failed
             azacitidine or decitabine will be eligible for this study, they will be analyzed
             separately from patients who have not received these drugs

          -  Treatment related mortality (TRM) score < 22.9; patients with TRM scores > 13.1, in
             whom the risk of death within 28 days of beginning induction therapy has averaged 41%,
             will preferentially be placed on protocol 2642

          -  Provision of written informed consent

          -  Note, unlike pharmaceutical company sponsored protocols eligibility is not conditioned
             on bilirubin, creatinine, or absence of other malignancy within the past 2-3 years;
             the TRM score incorporates creatinine and thus a high creatinine can in principle be
             offset by favorable values for the other covariates in the TRM score; bilirubin was
             not a covariate in the TRM; furthermore, in the doses we are using, dose adjustment of
             decitabine or ara-C is not indicated in the presence of renal or hepatic
             abnormalities; our broad eligibility criteria may increase the likelihood that our
             results will be generalizable; the inability to reproduce results of early phase AML
             studies has been a problem in the past
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival of Patients Over Age 60 With Newly Diagnosed AML/High Risk MDS
Time Frame:At 6 months
Safety Issue:
Description:Compared to historical data of a completed Southwestern Oncology Group (SWOG) trial of azacitidine and gemtuzumab ozogamicin.

Secondary Outcome Measures

Measure:Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Rate of Complete Response or Complete Response with Incomplete Count Recovery

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:University of Washington

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