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Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (FLAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00488709
Recruitment Status : Completed
First Posted : June 20, 2007
Last Update Posted : November 18, 2008
Information provided by:
PETHEMA Foundation

Tracking Information
First Submitted Date  ICMJE June 1, 2007
First Posted Date  ICMJE June 20, 2007
Last Update Posted Date November 18, 2008
Study Start Date  ICMJE May 2003
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2007)
  • To treat with the combination FLAT patients with acute myeloid leukaemia that they present a primary resistance [ Time Frame: one month ]
  • •To treat with the combination FLAT a relapse in the first 12 months after reach the first CR with standard treatment [ Time Frame: one month ]
  • To treat with combination FLAT patients can't receive the standard treatment due any cause [ Time Frame: one month ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00488709 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2007)
  • Improve the interval free survival and global survival [ Time Frame: one year ]
  • To avoid the toxicities produced by other chemotherapy in this type of patients [ Time Frame: 4 months ]
  • To determine the existing association between the response to the treatment with FLAT and the expression of Multi Drug Resistance (MDR) in the acute myeloid leukaemia [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official Title  ICMJE FLAT: Fludarabine, Cytarabine and Topotecan in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
Brief Summary

The study is designed with drugs used frequently in the treatment of AML, but with a new combination less toxic,and effective in AML multidrug resistant.


  • The AML patients with primary resistance or relapsed in the first 12 months after CR, have second line chemotherapy low response rate .
  • These patients with AML with primary resistance or relapse, that reach remission after a rescue treatment, have an interval free survival and a global survival very short
  • Probably the resistance to the treatments is in relation to different forms expression of the MDR.
  • Complete remission is considered valid evaluation, because every patient who should obtain a CR can be considered to be eligible for a possible curative treatment: Ara-C administration to high doses or the TPH treatment
Detailed Description

It is a protocol opened, multicentric, led to end to increase a) the rate of complete responses, b) the duration of the response, c) the free survival of disease and d) the global survival.

The included subjects will be patients with primary or secondary AML that they have not achieved the CR after the standard treatment with an anthracycline or derivative associated with Ara-C or have relapsed in the first 12 months after having achieved the RC. Also patients with AML that, for any reason, they could not receive the standard treatment with anthracycline and Ara-C, will be included

Cycle of induction. The patients will be treated by FLAT according to the following scheme:

  • FLUDARABINE, 30 mg/m2 i.v. (In 1 hour) on the 1st to 4.
  • CITARABINE, 2 g/m2 i.v. (In 4 hours), four hours after finishing the fludarabine, on the 1st to 4.
  • TOPOTECAN, 1,5 mg/m2 i.v. (In 4 hours), four hours after finishing the cytarabine, on the 1st to 4.

When the patient starts recovering the hematological counts, and providing that has not blasts in the peripheral blood (SP), he will become a medullar revision (MO):

  • If MO presents severe hypocellularity without blasts,no therapeutic measurement will take and there will repeat revisions weekly and MDR's study up to the CR or the blasts appearance.
  • If in MO persist blasts (>5 %) but have diminished less than 50 % of the initial number, the induction will be continued by the FLAT's second shift.
  • If in MO persists more than 50 % of blasts of the initial number, the patient goes out of the protocol and it will be treated as an agreement by the criterion of the center.

The patients who have managed to enter CR will receive a cycle of consolidation as soon as possible and always within 2 months from the day in which they received first FLAT's dose. The cycle of consolidation consists of another FLAT's scheme to the same doses.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Topotecan
  • Drug: Fludarabine
  • Drug: Cytarabine
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 19, 2007)
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects of 18 years of age or major, with diagnosis of primary or secondary AML, confirmed cytologically, that fulfill one of the following conditions:

    • Do not reach a CR after the conventional treatment.
    • Relapse in the first 12 months after a CR. During remission, patients can have be treated by a transplant. The relapse is defined as the presence of blasts in peripheric blood or the presence of >5 % of blasts in MO.
    • Not participation in a clinical trial.
  2. ECOG < o = 2
  3. Considered suitable patients for an intensive chemotherapy
  4. Informed consent

Exclusion Criteria:

  1. Pelvic or spinal radiotherapy in 4 weeks before the incorporation in the protocol.
  2. Acute promyelocytic leukaemia
  3. First line chemotherapy for AML which has contained fludarabine or topotecan.
  4. Active or chronic hepatitis or hepatic cirrhosis.
  5. Positivity known to the virus of the human immunodeficiency (HIV)
  6. Pregnant or breastfeeding patients.
  7. Patients with deterioration of the functions hepatic or renal, defined for the following values base them of laboratory:

    • AST or ALT >2,5 times the top limit of the normality of the center (LSNC)
    • Alkaline phosphatase >2,5 times the LSNC
    • Total bilirubin value >2 times the LSNC
    • Creatinine value >2 times the LSNC after a suitable hydration
  8. Precedents of intervention of major surgery in 2 weeks before the incorporation in the protocol.
  9. Patients with disease serious or not controlled (for example not controlled diabetes, infection, hypertension, etc.).
  10. Patients who have received other cytotoxic drugs (except hydroxyurea to reduce the leucocytosis) as treatment of the current relapse or of the resistance, in 4 weeks before the protocol.
  11. Patients with hypersensitivity known to someone of the drugs of the protocol.
  12. Patients treated previously with growth factors with purposes of sensibilization.
  13. Patients with psychological, intellectual or sensitive dysfunction that can reduce his capacity of comprehension and fulfillment of the protocol.
  14. Patients treated before with FLAT.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00488709
Other Study ID Numbers  ICMJE LAMR 2003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE PETHEMA Foundation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Bueno Javier, Dr Hospital Vall d'Hebron
Principal Investigator: Sanchez Eva, Dr Hospital Vall d'Hebron
PRS Account PETHEMA Foundation
Verification Date November 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP