Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT ID: NCT00488709
Last Updated: 2008-11-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE4
47 participants
INTERVENTIONAL
2003-05-31
2007-04-30
Brief Summary
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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
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Interventions
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Topotecan
Fludarabine
Cytarabine
Eligibility Criteria
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Inclusion Criteria
* 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
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.
18 Years
ALL
No
Sponsors
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PETHEMA Foundation
OTHER
Principal Investigators
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Bueno Javier, Dr
Role: STUDY_CHAIR
Hospital Vall d'Hebron
Sanchez Eva, Dr
Role: PRINCIPAL_INVESTIGATOR
Hospital Vall d'Hebron
Locations
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Hospital Juan Canalejo
A Coruña, , Spain
Hospital Ntra. Sra. de Sonsoles
Ávila, , Spain
Hospital germans Trias i Pujol
Badalona, , Spain
Centro Médico Teknon
Barcelona, , Spain
Hospital Sant Pau
Barcelona, , Spain
Hospital Vall d'Hebron
Barcelona, , Spain
Hospital General Yagüe
Burgos, , Spain
Hospital de Jerez
Cadiz, , Spain
Complejo hospitalario Xeral-Calde
Lugo, , Spain
Hospital Clínico Universitario San Carlos
Madrid, , Spain
Hospital Ramón y Cajal
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
Countries
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References
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Keating MJ, Kantarjian H, Smith TL, Estey E, Walters R, Andersson B, Beran M, McCredie KB, Freireich EJ. Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol. 1989 Aug;7(8):1071-80. doi: 10.1200/JCO.1989.7.8.1071.
Nussler V, Pelka-Fleischer R, Zwierzina H, Nerl C, Beckert B, Gieseler F, Diem H, Ledderose G, Gullis E, Sauer H, Wilmanns W. P-glycoprotein expression in patients with acute leukemia-clinical relevance. Leukemia. 1996 Jul;10 Suppl 3:S23-S31.
Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res. 1992 Apr 15;52(8):2268-78.
Michelutti A, Michieli M, Damiani D, Melli C, Ermacora A, Grimaz S, Candoni A, Russo D, Fanin R, Baccarani M. Effect of fludarabine and arabinosylcytosine on multidrug resistant cells. Haematologica. 1997 Mar-Apr;82(2):143-7.
Leoni F, Ciolli S, Nozzoli C, Santini V, Fanci R, Rossi Ferrini P. Fludarabine, cytarabine and topotecan (FLAT) as induction therapy for acute myeloid leukemia in the elderly: a preliminary report. Haematologica. 2001 Jan;86(1):104. No abstract available.
Frewin RJ, Johnson SA. The role of purine analogue combinations in the management of acute leukemias. Hematol Oncol. 2001 Dec;19(4):151-7. doi: 10.1002/hon.686.
Seiter K, Feldman EJ, Halicka HD, Traganos F, Darzynkiewicz Z, Lake D, Ahmed T. Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia. J Clin Oncol. 1997 Jan;15(1):44-51. doi: 10.1200/JCO.1997.15.1.44.
Sierra J, Brunet S, Granena A, Olive T, Bueno J, Ribera JM, Petit J, Besses C, Llorente A, Guardia R, Macia J, Rovira M, Badell I, Vela E, Diaz de Heredia C, Vivancos P, Carreras E, Feliu E, Montserrat E, Julia A, Cubells J, Rozman C, Domingo A, Ortega JJ. Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation. J Clin Oncol. 1996 Apr;14(4):1353-63. doi: 10.1200/JCO.1996.14.4.1353.
Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994 Oct 6;331(14):896-903. doi: 10.1056/NEJM199410063311402.
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Related Links
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Spanish association of Haematology
Other Identifiers
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FLAT
Identifier Type: -
Identifier Source: secondary_id
LAMR 2003
Identifier Type: -
Identifier Source: org_study_id