Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00136084
First received: August 24, 2005
Last updated: November 2, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to compare the effectiveness of two multi-agent chemotherapy regimens using different dosages of cytarabine to eliminate all detectable leukemia.


Condition Intervention Phase
Leukemia, Myelocytic, Acute
Drug: Cladribine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone
Drug: Etoposide, Cytarabine, Gemtuzumab, L-asparaginase, Mercaptopurine, methotrexate, Mitoxantrone, Prednisone, Vincristine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Minimal Residual Disease (MRD). [ Time Frame: Day 22 MRD measurement ] [ Designated as safety issue: No ]
    Detection of Minimal Residual Disease following one course of chemotherapy where positive MRD was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (>=0.1%).


Secondary Outcome Measures:
  • Proportion of Minimal Residual Disease (MRD)+ Patients Who Become MRD- After One Course of Gemtuzumab Ozogamicin (GO) [ Time Frame: Consolidation I ] [ Designated as safety issue: No ]
    To estimate the proportion of minimal residual disease (MRD)+ patients who become MRD- after one course of gemtuzumab ozogamicin (GO)

  • Proportion of MRD Reduction After One Course of Cytarabine + Daunomycin + Etoposide (ADE) + GO [ Time Frame: Induction II ] [ Designated as safety issue: No ]
    To estimate proportion of patients with MRD reduction after one course of Induction II (cytarabine + daunomycin + etoposide (ADE) + GO), who had no response to first course of induction therapy.

  • Proportion of Patients Experienced Toxicity of Cytarabine + Daunomycin + Etoposide (ADE) + GO. [ Time Frame: Induction II ] [ Designated as safety issue: No ]
    To estimate proportion of patients experiencing CTC Grade 3 or 4 toxicity during Induction II (Cytarabine + Daunomycin + Etoposide (ADE) + GO), who had no response to first course of induction therapy

  • To Estimate the Overall Event-free Survival (EFS) of AML Patients Who Undergo Risk-adapted and Genotype-directed Therapy [ Time Frame: Five Year ] [ Designated as safety issue: No ]
    Overall event-free survival (EFS) was defined as the time from study enrollment to induction failure, relapse, secondary malignancy, death, or study withdrawal for any reason, with event-free patients censored on the date of the last follow-up

  • To Assess Whether Inhibition of DNA Synthesis is Greater After High-dose Ara-C (HDAC) Than After Low-dose Ara-C (LDAC) Therapy [ Time Frame: Measurements were assessed in Induction I chemotherapy ] [ Designated as safety issue: No ]
    Inhibition of DNA synthesis is defined as the percentage of DNA synthesis rate at 24-hour post-araC treatment over DNA synthesis rate pre-araC treatment.

  • Relationship of Inhibition of DNA Synthesis and Clinical Response [ Time Frame: Measurements were assessed in Induction I chemotherapy ] [ Designated as safety issue: No ]
    Clinical response is defined as MRD (minimal residual disease) measured by flow cytometry at day 22. The MRD at day 22 is classified as positive (with MRD) or negative (no detectable MRD). The relation between inhibition of DNA synthesis and MRD was performed by logistic regression. In the model, logit of probability of MRD positive was regressed on inhibition of DNA synthesis.


Enrollment: 238
Study Start Date: August 2002
Study Completion Date: June 2012
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HDAC (High-Dose Cytarabine)
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Drug: Cladribine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone
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Experimental: LDAC (Low-Dose Cytarabine)
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Drug: Etoposide, Cytarabine, Gemtuzumab, L-asparaginase, Mercaptopurine, methotrexate, Mitoxantrone, Prednisone, Vincristine
Since limited characters are allowed in this passage, please see detailed Description to know the dosage, dosage form, frequency of administration for the above mentioned drugs

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia by immunophenotyping, morphology, and cytochemical staining; myelodysplasia; or biphenotypic leukemia.
  • Age less than or equal to 21 years at time of study entry.
  • No prior therapy for this malignancy (patients with secondary AML following treatment of primary malignancy are eligible) except for one dose of intrathecal therapy.
  • Negative pregnancy test
  • Patient does not have Down syndrome, acute promyelocytic leukemia (APL), or juvenile myelomonocytic leukemia (JMML)

Exclusion Criteria:

  • Positive pregnancy test
  • Down syndrome, acute promyelocytic leukemia (APL), or juvenile myelomonocytic leukemia (JMML)
  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: NCT00136084

Locations
United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hospital of Michigan (Wayne State University)
Detroit, Michigan, United States, 48201
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Children's Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Jeffrey Rubnitz, M.D., PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided by St. Jude Children's Research Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00136084     History of Changes
Other Study ID Numbers: AML02, 5R01CA113482
Study First Received: August 24, 2005
Results First Received: March 5, 2010
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Leukemia,Erythroblastic, Acute
Erythroblastic Leukemia, Acute
Leukemia, Myeloid, Acute
Myeloid Leukemia, Acute

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
6-Mercaptopurine
Cytarabine
Methotrexate
Cyclophosphamide
Cladribine
Gemtuzumab
Asparaginase
Daunorubicin
Dexamethasone
Etoposide
Mitoxantrone
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 11, 2014