Glivec in Ph Positive Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Positive Ph Acute Lymphoblastic Leucemia With Intensive Induction Chemotherapy and Glivec, Before and After the Hematopoetic Progenitor Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00388895
• Other study ID #: CSTI571BES02
• Secondary ID: 02-0207 (nº AEMP
• Status: Completed
• Phase: Phase 2
• First received: October 16, 2006
• Last updated: November 17, 2008
• Start date: June 2002
• Est. completion date: October 2007

Study information

• Verified date: November 2008
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

% positive Ph LLA with RC alter the Glivec and induction chemotherapy treatment

Description:

Pilot phase II clinical trial, prospective, multicentric and opened

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 2007
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

Inclusion Criteria:

• New diagnosis LLA Ph+ (BCR/ABL) patients = 65 years old

• Fertile age women must do a pregnancy test in the 7 days previous at the beginning of clinical trial medication

• Performance status 0-2 (Appendix B); Is allowed performance status > 2 because of LLA

• Patients without organ alteration: hepatic function: global bilirubin, AST, ALT, gamma-GT and alkaline phosphatase less than 2 times LSN; renal function: Creatinine < 1,5 mg/dl o Clearance creatinine > 60 ml/min; anormal renal function caused by LLA ; normal heart function (Appendix B): FEV > 50%; No Chronic respiratory illness. If the anormal values are secondary of the experimental illness the investigator can decide himself if the patient can be included at the clinical trial.

• Negative HIV serology

• Written, oral or with witness informed consent. In patients < 18 years old must be signed written and legal representative informed consent.

• No experimental chemotherapy or other experimental treatment. Allowed to begin induction chemotherapy from the diagnosis to confirm Ph. No major surgical process in the previous 14 days of the treatment Start.

Exclusion Criteria:

• Other LLA variability

• Previous history of coronary valvular, hypertensive cardiopathy illness

• Chronic hepatic illness

• Chronic respiratory insufficiency

• Renal insufficiency not caused by LLA

• Severe neurological problems not caused by LLA

• Severe affection of the performance status (grade 3-4 OMS gradation) not caused by LLA

• Pregnancy and women

• Blastic crisis LMC

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Cromosome Philadelphia Positive
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• chemotherapy

• Glivec

Locations

Country	Name	City	State
Spain	Hospital General de Alicante	Alicante
Spain	Hospital "Duran I Reynals"	Barcelona
Spain	Hospital "Santa Creu i Sant Pau"	Barcelona
Spain	Hospital Clínico y Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario "Germans Trias i Pujol"	Barcelona
Spain	Hospital Valle Hebrón	Barcelona
Spain	Hospital Valle Hebrón-Materno Infantil	Barcelona
Spain	Hospital Puerta del Mar	Cádiz
Spain	Hospital Juan Canalejo	La Coruña
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Clínico San Carlos de Madrid	Madrid
Spain	Hospital Doce de Octubre	Madrid
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	. Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Carlos Haya	Málaga
Spain	Hospital General Universitario Morales Meseguer.	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Son Dureta	Palma de Mallorca
Spain	Hospital Son Llàtzer	Palma de Mallorca
Spain	Clínica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Aricò M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, Gaynon P, Silverman L, Janka-Schaub G, Kamps W, Pui CH, Masera G. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med. 2000 Apr 6;342(14):998-1006. — View Citation

Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001 Apr 5;344(14):1038-42. Erratum in: N Engl J Med 2001 Jul 19;345(3):232. — View Citation

Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996 May;2(5):561-6. — View Citation

Gambacorti-Passerini C, Barni R, le Coutre P, Zucchetti M, Cabrita G, Cleris L, Rossi F, Gianazza E, Brueggen J, Cozens R, Pioltelli P, Pogliani E, Corneo G, Formelli F, D'Incalci M. Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst. 2000 Oct 18;92(20):1641-50. — View Citation

le Coutre P, Tassi E, Varella-Garcia M, Barni R, Mologni L, Cabrita G, Marchesi E, Supino R, Gambacorti-Passerini C. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000 Mar 1;95(5):1758-66. — View Citation

Mahon FX, Deininger MW, Schultheis B, Chabrol J, Reiffers J, Goldman JM, Melo JV. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood. 2000 Aug 1;96(3):1070-9. — View Citation

Mitterbauer G, Nemeth P, Wacha S, Cross NC, Schwarzinger I, Jaeger U, Geissler K, Greinix HT, Kalhs P, Lechner K, Mannhalter C. Quantification of minimal residual disease in patients with BCR-ABL-positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction. Br J Haematol. 1999 Sep;106(3):634-43. — View Citation

Saffroy R, Lemoine A, Brézillon P, Frénoy N, Delmas B, Goldschmidt E, Souleau B, Nedellec G, Debuire B. Real-time quantitation of bcr-abl transcripts in haematological malignancies. Eur J Haematol. 2000 Oct;65(4):258-66. — View Citation

Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig WD, Henze G, Gadner H, Odenwald E, Riehm H. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Münster. Leukemia. 2000 Dec;14(12):2205-22. — View Citation

Snyder DS, Nademanee AP, O'Donnell MR, Parker PM, Stein AS, Margolin K, Somlo G, Molina A, Spielberger R, Kashyap A, Fung H, Slovak ML, Dagis A, Negrin RS, Amylon MD, Blume KG, Forman SJ. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999 Dec;13(12):2053-8. — View Citation

Tabernero MD, Bortoluci AM, Alaejos I, López-Berges MC, Rasillo A, García-Sanz R, García M, Sayagués JM, González M, Mateo G, San Miguel JF, Orfao A. Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expresssion. Leukemia. 2001 Mar;15(3):406-14. — View Citation

Thomas X, Thiebaut A, Olteanu N, Danaïla C, Charrin C, Archimbaud E, Fiere D. Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther. 1998 Jun;40(3):119-28. — View Citation

Weisberg E, Griffin JD. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines. Blood. 2000 Jun 1;95(11):3498-505. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	% positive Ph LLA with RC alter the Glivec and induction chemotherapy treatment.
Primary	Discover if is possible to treat patients with Glivec plus Standard consolidation treatment.
Primary	Discover the Glivec effect over ERM during consolidation treatment and alter transplant

External Links

•   Pethema Foundation web
•   Spanish association of Haematology