Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Followed By Peripheral Stem Cell Transplantation or Isotretinoin in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Acute Lymphocytic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 19 to 90 Other AUH-MCP-70612-01 AUH-MCP-70612-02P, NCI-V98-1485, NCT00003619

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.

Entry 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

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

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

Expected Enrollment

A total of 15 patients will be accrued for this study within 3-4 years.

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.

Besa E, Maiale C, Liman D, et al.: Early data on a new combination chemotherapy using topotecan, fludarabine, ARA-C and G-CSF for aggressive myelodysplastic syndromes in the elderly. [Abstract] Leuk Res 23 (Suppl 1): A-191, S72, 1999.

Trial Contact Information

Trial Lead Organizations

Drexel University College of Medicine - Center City Hahnemann Campus

Emmanuel Besa, MD, Protocol chair(Contact information may not be current)		Ph: 215-762-8288

Registry Information
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
Trial Start Date		1998-02-17
Registered in ClinicalTrials.gov		NCT00003619
Date Submitted to PDQ		1998-10-05
Information Last Verified		2008-02-27

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