Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
Intervention: cytarabine (Drug); daunorubicin hydrochloride (Drug); etoposide (Drug); filgrastim (Drug); fludarabine phosphate (Drug); tretinoin (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Medical Research Council Official(s) and/or principal investigator(s):
D. W. Milligan, MD, Study Chair, Affiliation: Birmingham Heartlands Hospital
Summary
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.
Clinical Details
Official title: Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML
Study design: Treatment, Randomized, Active Control
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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Birmingham Heartlands Hospital, Birmingham, England B9 5SS, United Kingdom
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Related 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.
Starting date: August 1998
Last updated: May 23, 2008
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