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

NCT00488709 | Completed Phase 4 DMC

• 2 other identifiers: LAMR 2003FLAT
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 16

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. 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

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Multi Drug Resistance

Outcome Measures

Primary Outcomes (3)

• To treat with the combination FLAT patients with acute myeloid leukaemia that they present a primary resistance

  one month

• •To treat with the combination FLAT a relapse in the first 12 months after reach the first CR with standard treatment

  one month

• To treat with combination FLAT patients can't receive the standard treatment due any cause

  one month

Secondary Outcomes (3)

• Improve the interval free survival and global survival

  one year

• To avoid the toxicities produced by other chemotherapy in this type of patients

  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

  6 months

Interventions

Topotecan DRUG

Fludarabine DRUG

Cytarabine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG \< o = 2
• Considered suitable patients for an intensive chemotherapy
• Informed consent

You may not qualify if:

• Pelvic or spinal radiotherapy in 4 weeks before the incorporation in the protocol.
• Acute promyelocytic leukaemia
• First line chemotherapy for AML which has contained fludarabine or topotecan.
• Active or chronic hepatitis or hepatic cirrhosis.
• Positivity known to the virus of the human immunodeficiency (HIV)
• Pregnant or breastfeeding patients.
• 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
• Precedents of intervention of major surgery in 2 weeks before the incorporation in the protocol.
• Patients with disease serious or not controlled (for example not controlled diabetes, infection, hypertension, etc.).
• 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.
• Patients with hypersensitivity known to someone of the drugs of the protocol.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (16)

Hospital Juan Canalejo

A Coruña, Spain

Location

Hospital Ntra. Sra. de Sonsoles

Ávila, Spain

Location

Hospital germans Trias i Pujol

Badalona, Spain

Location

Centro Médico Teknon

Barcelona, Spain

Location

Hospital Sant Pau

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital General Yagüe

Burgos, Spain

Location

Hospital de Jerez

Cadiz, Spain

Location

Complejo hospitalario Xeral-Calde

Lugo, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hosptal Joan XXIII

Tarragona, Spain

Location

Hospital Verge de la Cinta

Tortosa, Spain

Location

Hospital Rio Hortega

Valladolid, Spain

Location

Hospital Clinico Lozano Blesa

Zaragoza, Spain

Location

Related Publications (18)

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• Rees JK, Gray RG, Swirsky D, Hayhoe FG. Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial. Lancet. 1986 Nov 29;2(8518):1236-41. doi: 10.1016/s0140-6736(86)92674-7.

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• Vey N, Keating M, Giles F, Cortes J, Beran M, Estey E. Effect of complete remission on survival in patients with acute myelogenous leukemia receiving first salvage therapy. Blood. 1999 May 1;93(9):3149-50. No abstract available.

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  PMID: 9402325 BACKGROUND

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  PMID: 2666590 BACKGROUND

• 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.

  PMID: 8656697 BACKGROUND

• 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.

  PMID: 1348448 BACKGROUND

• 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.

  PMID: 9175315 BACKGROUND

• 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.

  PMID: 11146581 BACKGROUND

• 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.

  PMID: 11754391 BACKGROUND

• 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.

  PMID: 8996123 BACKGROUND

• 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.

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  PMID: 8823330 BACKGROUND

Related Links

• Spanish association of Haematology

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Topotecan; fludarabine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bueno Javier, Dr

  Hospital Vall d'Hebron

  STUDY CHAIR

• Sanchez Eva, Dr

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 1, 2007
• First Posted: June 20, 2007
• Study Start: May 1, 2003
• Study Completion: April 1, 2007
• Last Updated: November 18, 2008

Record last verified: 2008-11

Locations

ES (16)