- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00005863
Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia
Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether combination chemotherapy with filgrastim and/or tretinoin is more effective than combination chemotherapy alone for acute myeloid leukemia.
PURPOSE: This randomized phase III trial is studying combination chemotherapy with filgrastim and/or tretinoin to see how well they work compared to combination chemotherapy alone in treating patients with acute myeloid leukemia.
Study Overview
Status
Detailed Description
OBJECTIVES:
- Compare standard induction chemotherapy with cytarabine, daunorubicin, and etoposide vs fludarabine and cytarabine in terms of achievement of remission, reasons for remission failure, duration of remission, survival, toxicity, and supportive care needs in patients with high risk acute myeloid leukemia.
- Determine if the use of filgrastim (G-CSF) or tretinoin administered during and following chemotherapy improves outcome in this patient population.
- Determine the impact of these treatment regimens on quality of life in these patients.
OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to type of disease (resistant vs refractory vs relapsed vs adverse cytogenetic), age (under 15 vs 15 to 29, vs 30 to 49 vs 50-59 vs 60-69 vs 70 and over), performance status, and de novo and secondary leukemia. Patients with relapsed disease are further stratified according to duration of first remission (less than 6 months vs 6 to 12 months vs 12 months and over), and prior transplantation (yes vs no).
Patients are randomized into one of two treatment arms for induction chemotherapy.
- Arm I: Patients receive induction chemotherapy consisting of cytarabine IV every 12 hours on days 1-10, daunorubicin IV on days 1, 3, and 5 and etoposide IV over 1 hour on days 1-5. Patients receive a second course of therapy with cytarabine IV every 12 hours on days 1-8 and daunorubicin and etoposide as in course 1.
- Arm II: Patients receive 2 courses of induction chemotherapy consisting of fludarabine IV over 30 minutes followed by cytarabine IV over 4 hours on days 1-5.
Patients are further randomized into one of two treatment arms for colony stimulating factor therapy.
- Arm I: Patients receive filgrastim (G-CSF) subcutaneously or IV daily beginning on day 1 of each course of induction chemotherapy and continuing until blood counts recover, for up to a maximum of 28 days.
- Arm II: Patients receive no G-CSF during and following induction chemotherapy. Patients are further randomized into one of two treatment arms for retinoid therapy.
- Arm I: Patients receive oral tretinoin daily beginning on day 1 of induction chemotherapy and continuing for up to a maximum of 90 days.
- Arm II: Patients receive no retinoid therapy during and following induction chemotherapy.
Following completion of induction chemotherapy, patients achieving complete remission and blood count recovery may receive subsequent therapy consisting of consolidation chemotherapy and/or autologous or allogeneic transplantation.
Quality of life is assessed at 3 months.
PROJECTED ACCRUAL: Approximately 800-1,000 patients will be accrued for this study within 4-5 years.
Study Type
Phase
- Phase 3
Contacts and Locations
Study Locations
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England
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Birmingham, England, United Kingdom, B9 5SS
- Birmingham Heartlands Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Diagnosis of acute myeloid leukemia (AML) including de novo or secondary AML, or a preexisting myelodysplastic syndrome
- Overt resistant disease with more than 15% bone marrow blasts after induction course
Primary refractory disease
- Failure to achieve first complete remission after at least 2 induction courses
- Relapse from first remission with more than 5% bone marrow blasts
- Complete or partial remission following 1 induction course with adverse cytogenetic abnormalities at diagnosis
- No acute promyelocytic leukemia
- No chronic myeloid leukemia in blast transformation
- No prior relapse from a second or greater remission
PATIENT CHARACTERISTICS:
Age:
- Any age
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Not specified
Renal:
- Creatinine clearance at least 30 mL/min
Other:
- No other active malignancy
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: D. W. Milligan, MD, University Hospital Birmingham NHS Foundation Trust
Publications and helpful links
General Publications
- Burnett AK, Milligan D, Hills RK, et al.: Does all-transretinoic acid (ATRA) have a role in non-APL acute myeloid leukaemia? Results from 1666 patients in three MRC trials. [Abstract] Blood 104 (11): A-1794, 2004.
- Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. doi: 10.1182/blood-2005-10-4202. Epub 2006 Feb 16.
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- 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)
- secondary acute myeloid leukemia
- childhood acute myeloid leukemia in remission
- childhood myelodysplastic syndromes
- recurrent adult acute myeloid leukemia
- adult acute myeloid leukemia in remission
- adult acute erythroid leukemia (M6)
- adult acute megakaryoblastic leukemia (M7)
- adult acute minimally differentiated myeloid leukemia (M0)
- adult acute monoblastic leukemia (M5a)
- adult acute monocytic leukemia (M5b)
- adult acute myeloblastic leukemia with maturation (M2)
- adult acute myeloblastic leukemia without maturation (M1)
- adult acute myelomonocytic leukemia (M4)
- recurrent childhood acute myeloid leukemia
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- childhood acute erythroleukemia (M6)
- childhood acute megakaryocytic leukemia (M7)
- childhood acute minimally differentiated myeloid leukemia (M0)
- atypical chronic myeloid leukemia, BCR-ABL1 negative
- childhood acute myeloblastic leukemia without maturation (M1)
- childhood acute myeloblastic leukemia with maturation (M2)
- childhood acute myelomonocytic leukemia (M4)
- childhood acute monoblastic leukemia (M5a)
- childhood acute monocytic leukemia (M5b)
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Keratolytic Agents
- Etoposide
- Fludarabine
- Fludarabine phosphate
- Cytarabine
- Daunorubicin
- Tretinoin
Other Study ID Numbers
- CDR0000067895
- MRC-LEUK-AML-HR
- EU-20008
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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