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
19 Years
90 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Thrombocytopenia
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Emmanuel C. Besa, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Drexel University College of Medicine
Authority:
United States: Federal Government
Study ID:
AUH-MCP-70612-01
NCT ID:
NCT00003619
Start Date:
February 1998
Completion Date:
April 2004
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Myelodysplastic Syndromes
- Thrombocytopenia
- recurrent adult acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- relapsing chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- polycythemia vera
- primary myelofibrosis
- refractory anemia
- refractory anemia with ringed sideroblasts
- refractory anemia with excess blasts
- chronic myelomonocytic leukemia
- secondary acute myeloid leukemia
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- thrombocytopenia
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Thrombocytopenia
Name | Location |
|---|---|
| Medical College of Pennsylvania | Philadelphia, Pennsylvania 19129 |
| Medical College of Pennsylvania Hospital | Philadelphia, Pennsylvania 19129 |
