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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003619
First received: November 1, 1999
Last updated: June 25, 2013
Last verified: February 2008
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Myelodysplastic Syndromes
Thrombocytopenia
Biological: filgrastim
Dietary Supplement: vitamin E
Drug: busulfan
Drug: cytarabine
Drug: etoposide
Drug: fludarabine phosphate
Drug: isotretinoin
Drug: topotecan hydrochloride
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: February 1998
Study Completion Date: April 2004
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

Ages Eligible for Study:   19 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003619

Locations
United States, Pennsylvania
Medical College of Pennsylvania
Philadelphia, Pennsylvania, United States, 19129
Medical College of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19129
Sponsors and Collaborators
Drexel University College of Medicine
Investigators
Study Chair: Emmanuel C. Besa, MD Drexel University College of Medicine
  More Information

Additional Information:
Publications:
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.

ClinicalTrials.gov Identifier: NCT00003619     History of Changes
Other Study ID Numbers: AUH-MCP-70612-01, CDR0000066698, AUH-MCP-70612-02P, NCI-V98-1485
Study First Received: November 1, 1999
Last Updated: June 25, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Thrombocytopenia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Blood Platelet Disorders
Busulfan
Cytarabine
Fludarabine phosphate
Fludarabine
Etoposide
Topotecan
Lenograstim
Vidarabine
Isotretinoin
Vitamin E
Vitamins

ClinicalTrials.gov processed this record on August 20, 2014