Combination Chemotherapy Followed By Peripheral Stem Cell Transplantation or Isotretinoin in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Acute Lymphocytic 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: Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Thrombocytopenia
Intervention: busulfan (Drug); cytarabine (Drug); etoposide (Drug); filgrastim (Drug); fludarabine phosphate (Drug); isotretinoin (Drug); topotecan hydrochloride (Drug); vitamin E (Drug); bone marrow ablation with stem cell support (Procedure); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: Drexel University Official(s) and/or principal investigator(s):
Emmanuel C. Besa, MD, Study Chair, Affiliation: Drexel University
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to
give higher doses of chemotherapy drugs and kill more cancer cells. Isotretinoin may help
cancer cells develop into normal white blood cells.
PURPOSE: Phase I/II trial of topotecan, fludarabine, cytarabine, and filgrastim followed by
peripheral stem cell transplantation or isotretinoin in treating patients who have acute
myeloid leukemia, myelodysplastic syndrome, or recurrent or refractory acute lymphocytic
leukemia.
Clinical Details
Official title: A Phase I/II Combination Study of Topotecan, Fludarabine, Cytosine Arabinoside and G-CSF (T-FLAG) Induction Therapy in Patients With Poor Prognosis AML, MDS and Relapsed/Refractory ALL Followed by Maintenance of Either PBSC Transplant or 13 Cis-Retinoic Acid
Study design: Treatment
Detailed description:
OBJECTIVES: I. Determine the safety of topotecan in combination with fludarabine, cytarabine,
and filgrastim (FLAG) in patients with poor prognosis acute myeloid leukemia, myelodysplastic
syndrome, or recurrent or refractory acute lymphocytic leukemia. II. Determine the maximum
tolerated dose of topotecan in the FLAG regimen in these patients. III. Assess the complete
remission rates in patients treated with this regimen.
OUTLINE: Patients with complete response proceed to further therapy according to age. 65 and
under: Patients receive etoposide by IV continuously for 5 days, cytarabine IV over 2 hours
every 12 hours for 4 days, and filgrastim (G-CSF) subcutaneously. Peripheral blood stem cells
(PBSC) are then harvested. Patients then receive oral busulfan every 6 hours on days - 7 to -4 and etoposide IV over 10 hours on day - 3. PBSC are reinfused on day 0. Over 65: Patients
receive oral isotretinoin and vitamin E daily. Treatment continues in the absence of disease
progression or unacceptable toxicity. Patients are followed every month for 1 year and then
every 3 months thereafter.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 3-4 years.
Eligibility
Minimum age: 19 Years.
Maximum age: 90 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS: Histologically proven poor prognosis acute myeloid leukemia (AML),
myelodysplastic syndrome (MDS), or recurrent/refractory acute lymphocytic leukemia,
including: Myelodysplastic syndrome (MDS) stages B and C Refractory anemia, refractory
anemia with ringed sideroblasts, or refractory anemia with excess blasts (between 5% and
20% myeloblasts) MDS with increased erythroblasts or monocytoblasts of no greater than 20%
MDS in transformation (between 20% to 30% myeloblasts) or acute nonlymphoblastic leukemia
(at least 30% myeloblasts) Chronic myelomonocytic leukemia Poor prognosis refractory or
recurrent acute myeloid leukemia after complete response Secondary or therapy related AML
or MDS AML blastic crisis of chronic myelogenous leukemia or other myeloproliferative
disorders such as polycythemia vera, essential thrombocytopenia, or agnogenic myeloid
metaplasia
PATIENT CHARACTERISTICS: Age: 19 to 90 Performance status: ECOG 0-2 Life expectancy: Not
specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2. 0 mg/dL SGOT or
SGPT less than 2. 0 times upper limit of normal Renal: Normal serum creatinine
Cardiovascular: No congestive heart failure No symptomatic ischemic heart disease Other:
Not pregnant or nursing Fertile patients must use effective contraception HIV negative No
uncontrolled infection No poorly controlled diseases (e. g., diabetes, systemic lupus
erythematosus) No history of psychiatric disorders No other malignancies within the past 5
years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of
the cervix No concurrent severe medical problems No history of allergic reaction to
topotecan and its derivatives
PRIOR CONCURRENT THERAPY: Biologic therapy: No other concurrent immunotherapy Chemotherapy:
No prior topotecan At least 4 weeks since prior chemotherapy No other concurrent
chemotherapy Endocrine therapy: Not specified Radiotherapy: No concurrent radiotherapy
Surgery: Not specified Other: No other investigational drugs within 30 days of study No
other concurrent investigational therapy except for basal cell skin cancer
Locations and Contacts
Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129, United States
Medical College of Pennsylvania Hospital, Philadelphia, Pennsylvania 19129, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: February 1998
Last updated: May 23, 2008
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