Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01041703
First received: December 31, 2009
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as clofarabine, daunorubicin hydrochloride, cytarabine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying clofarabine to see how well it works compared with daunorubicin hydrochloride and cytarabine when followed by decitabine or observation in treating older patients with newly diagnosed acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: clofarabine
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: decitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin & Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Followed by Decitabine Maintenance vs. Observation in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age >/= 60 Years)

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 30-day mortality rate [ Designated as safety issue: No ]
  • Induction complete response rates [ Designated as safety issue: No ]
  • Effect of decitabine as maintenance therapy vs observation on disease-free survival [ Designated as safety issue: No ]
  • Impact of consolidation therapy with non-myeloablative conditioning and allogeneic hematopoietic stem cell transplantation from HLA-identical sibling donor on overall survival in select patients [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 747
Study Start Date: January 2011
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (induction therapy)
Patients receive standard therapy comprising daunorubicin hydrochloride IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7.
Drug: cytarabine
Given IV
Drug: daunorubicin hydrochloride
Given IV
Experimental: Arm II (induction therapy)
Patients receive clofarabine IV over 1 hour on days 1-5.
Drug: clofarabine
Given IV
Active Comparator: Arm I (consolidation therapy)
Patients receive cytarabine IV over 1 hour once or twice daily on days 1-6. Treatment repeats every 4-6 weeks for 2 courses.
Drug: cytarabine
Given IV
Experimental: Arm II (consolidation therapy)
Patients receive clofarabine IV over 1 hour on days 1-5. Treatment repeats every 4-6 weeks for 2 courses.
Drug: clofarabine
Given IV
No Intervention: Arm I (maintenance therapy)
Patients undergo observation.
Experimental: Arm II (maintenance therapy)
Patients receive decitabine IV over 1 hour on days 1-3. Treatment repeats every 4 weeks for 12 months the absence of unacceptable toxicity.
Drug: decitabine
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute myeloid leukemia (AML)
  • Considered candidates for intensive chemotherapy based on examination of peripheral blood or bone marrow aspirate specimens or touch preparations of the bone marrow biopsy obtained within the past 2 weeks

    • Bone marrow aspirate is required for enrollment, however, if there is discordance between percentage of myeloblasts on the differential of the peripheral blood or aspirate, the peripheral blood criteria are sufficient for diagnosis
  • Patients with secondary AML (defined as AML that has developed in a person with a history of antecedent blood count abnormalities, myelodysplastic syndromes [MDS], or a myeloproliferative disorder [excluding chronic myeloid leukemia], or a history of prior chemotherapy or radiotherapy for a disease other than AML) are eligible
  • Patients with acute promyelocytic leukemia (APL) confirmed either by the presence of t(15;17)(q22;q21) or PML/RAR transcripts will be excluded
  • No blastic transformation of chronic myelogenous leukemia
  • No documented CNS involvement
  • Concurrent registration on ECOG-E3903 (Ancillary Laboratory Protocol for the Collecting of Diagnostic Samples from Patients With Leukemia or Related Hematologic Disorders Being Considered for ECOG Treatment Clinical Trials) required (except for patients participating at CTSU institutions; these patients are exempt from this requirement)

    • Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (>10^9/L) from peripheral blood
    • Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing
  • Peripheral blood stem cell donor meeting 1 of the following criteria:

    • HLA-identical sibling (6/6)

      • Low-resolution HLA typing (A,B,DR) allowed
    • Matched unrelated donor (10/10)

      • High-resolution class I and II typing (A,B,C,DRB1 and DQ) should be matched at all 10 loci

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-3 (ECOG PS 0-2 if ≥ 70 years of age)
  • AST and ALT ≤ grade 1
  • Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ grade 1)
  • Serum creatinine ≤ 1 mg/dL (≤ grade 1)
  • Cardiac ejection fraction ≥ 45% by MUGA or 2-D ECHO
  • Fertile patients must use effective contraception
  • No concurrent active malignancy requiring treatment (other than MDS)
  • No active, uncontrolled infection
  • No known HIV infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy for AML (except for hydroxyurea for increased blast count or leukapheresis for leukocytes)
  • No prior treatment with azacitidine, decitabine, or low-dose cytarabine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041703

  Show 235 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: James M. Foran, MD, FRCPC Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01041703     History of Changes
Other Study ID Numbers: CDR0000659585, ECOG-E2906
Study First Received: December 31, 2009
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with del(5q)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Clofarabine
Cytarabine
Daunorubicin
Decitabine
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014