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

This study has been completed.
Sponsor:
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00488709
First received: June 1, 2007
Last updated: November 17, 2008
Last verified: November 2008
  Purpose

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.

Justification:

  • 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

Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Topotecan
Drug: Fludarabine
Drug: Cytarabine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: FLAT: Fludarabine, Cytarabine and Topotecan in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 47
Study Start Date: May 2003
Study Completion Date: April 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488709

Locations
Spain
Hospital Juan Canalejo
A Coruña, Spain
Hospital Ntra. Sra. de Sonsoles
Avila, Spain
Hospital germans Trias i Pujol
Badalona, Spain
Centro Médico Teknon
Barcelona, Spain
Hospital Vall d'Hebron
Barcelona, Spain
Hospital Sant Pau
Barcelona, Spain
Hospital General Yagüe
Burgos, Spain
Hospital de Jerez
Cadiz, Spain
Complejo hospitalario Xeral-Calde
Lugo, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Clínico Universitario San Carlos
Madrid, Spain
Hospital Virgen de la Victoria
Málaga, Spain
Hosptal Joan XXIII
Tarragona, Spain
Hospital Verge de la Cinta
Tortosa, Spain
Hospital Rio Hortega
Valladolid, Spain
Hospital Clinico Lozano Blesa
Zaragoza, Spain
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Study Chair: Bueno Javier, Dr Hospital Vall d'Hebron
Principal Investigator: Sanchez Eva, Dr Hospital Vall d'Hebron
  More Information

Additional Information:
Publications:
3. Lister TA, Rohatiner AZS. The treatment of adult acute leukaemia in adults. Sem Hematol 1982; 19:172
19. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd: Intensive post-remission chemotherapy in adults with acute myeloid leukemia. New Engl J Med 1994; 331:896-903

ClinicalTrials.gov Identifier: NCT00488709     History of Changes
Other Study ID Numbers: LAMR 2003, FLAT
Study First Received: June 1, 2007
Last Updated: November 17, 2008
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Acute Myeloid Leukemia
Multi Drug Resistance

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Fludarabine
Fludarabine phosphate
Topotecan
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014