Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old

Acute Myeloid Leukemia Clinical Trial

— LAM-SA 2007  

Official title:

Randomized Prospective Study of Adding Lomustine to Idarubicin and Cytarabine for Induction and Post-remission Chemotherapy in Older Patients With Acute Myeloid Leukaemia, and Feasibility of Allogeneic Transplantation for Patients From 60 to 65 Years Old

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00590837
• Other study ID #: CHUBX 2007/13
• Status: Completed
• Phase: Phase 3
• First received: December 27, 2007
• Last updated: April 1, 2014
• Start date: February 2008
• Est. completion date: December 2013

Study information

• Verified date: April 2014
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

A multicenter randomized trial comparing induction therapy (IC: Idarubicin and Cytarabine, 5 + 7) to ICL (the same drugs plus lomustine (CCNU), 200 mg/m2 orally at day 1). Patients in complete remission (CR) will then receive a post-remission schedule with or without lomustine according to randomization. Patients from 60 to 65 years old will be proposed to reduced conditioning allogeneic transplantation after first consolidation.

Description:

• Principal Objective: The primary objective of this study is to assess the ability of lomustine to increase the overall survival by adding lomustine to induction and post-remission chemotherapy.

• Secondary Objectives:

• To assess the ability of lomustine to increase the CR rate.

• To assess the ability of lomustine to increase the event-free survival.

• To evaluate the toxicity and side-effects of lomustine.

• To evaluate the feasibility of reduced conditioning allogeneic transplantation *between 60 and 65 years old.

• To evaluate prognostic factors.

• To evaluate QOL in elderly.

• Study design: Parallel

• Study plan:

• Induction therapy: Patients will be randomized to receive idarubicin (5d) plus cytarabine or the same drugs plus lomustine, the latter given at the dose of 200 mg/m2 orally at day 1.

• Consolidation therapy: After completing induction treatment, patients who are in complete remission will receive a course of consolidation therapy with idarubicin (3d) and subcutaneous cytarabine.

• Maintenance therapy: In all patients with persisting CR one month after completing consolidation: six courses of monthly combination chemotherapy (idarubicin (1d) and subcutaneous cytarabine) and then a continuous regimen of methotrexate and 6-mercaptopurine, for 6 months.

• Allogeneic transplantation: Patients between 60 and 65 years old with a full matched donor will receive after consolidation (if still in CR) an alloBMT with a reduced conditioning regimen of Fludarabine (3d) and TBI (2Gy).

• Number of subjects: 460

Recruitment information / eligibility

• Status: Completed
• Enrollment: 459
• Est. completion date: December 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 60 years and older with de novo AML and non-poor cytogenetic features.

• Patients with no unfavourable cytogenetic (based on GOELAMS-BGMT criteria)

• Performance status and Sorror score < 3 .

• Signed and dated informed consent.

Exclusion Criteria:

• Acute promyelocytic leukemia.

• Patients with myeloproliferative syndromes prior to diagnosis of AML.

• Patients who previously had myelodysplastic syndrome.

• Positive serology for HIV.

• Patients with unfavourable cytogenetic

• Patients with an isolated medullary extra localization of their disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Lomustine
Induction: chemotherapy + lomustine (CCNU), 200 mg/m2 orally at day 1. Consolidation: chemotherapy + lomustine (CCNU), 80 mg orally at day 1. Reinductions: chemotherapy + lomustine (CCNU), 40 mg orally at day 1.

Locations

Country	Name	City	State
France	Services maladies du sang, cancérologie, Hôpital Sud, CHU Amiens	Amiens
France	Service des maladies du sang, Centre Hospitalier Universitaire d'Angers	Angers
France	Service Hématologie, Centre Hospitalier Annecy	Annecy
France	C.H Victor Dupouy	Argenteuil
France	Service Médecine Interne, Onco-Hématologie, Maladies Infectieuses, Hôpital Henri Duffaut, Centre Hospitalier Avignon	Avignon
France	Service Hématologie, Centre Hospitalier de la Côte Basque	Bayonne
France	Service Hématologie, Hôpital Minjoz	Besançon
France	Unité Hématologie, Centre Hospitalier Blois	Blois
France	Service des maladies du sang - Hôpital Haut-Lévêque	Bordeaux - Pessac
France	Service Hématologie, Hôpital Dr Duchenne	Boulogne-sur-Mer
France	Service Hématologie, Hôpital Augustin Morvan	Brest
France	Service Hématologie et Thérapie cellulaire, Pavillon Villemin Pasteur, CHU Clermont-Ferrand	Clermont-Ferrand
France	Service Oncologie - Hématologie, Hôpital Pasteur, Centre Hospitalier Colmar	Colmar
France	Service Hématologie Clinique, CHU Dijon Hôpital des enfants	Dijon
France	Service Hématologie Clinique, Hôpital Michallon, CHU de Grenoble	Grenoble
France	Service Onco-Hématologie 3, Institut Paoli Calmettes	Marseille
France	Service Hématologie Oncologie, CHR Metz-Thionville	Metz
France	Service Hématologie Oncologie, Hôpital Lapeyronie, CHU de Montpellier	Montpellier
France	Département d'hématologie, Hôpital E.Muller, Centre Hospitalier de Mulhouse	Mulhouse
France	Service Hématologie Clinique, CHU -Hôtel Dieu	Nantes
France	Service Hématologie Clinique, Hôpital Archet 1	Nice
France	Service Médecine B - Unité Onco-hématologique, CHU Caremeau	Nîmes
France	Service Oncologie Médicale, Hôpital de la Source	Orléans
France	Unité d'Hématologie, Hôpital Cochin	Paris
France	Service Hématologie, CHG Saint Jean	Perpignan
France	Service Hématologie Clinique, Hôpital Robert Debre	Reims
France	Service Hématologie Clinique, Hôpital Pontchaillou	Rennes
France	Service d'Hématologie, Institut de Cancérologhie de la Loire	Saint Priez en Jarez
France	Département d'Hématologie et d'Oncologie, Hôpital CHRU de Hautepierre	Strasbourg
France	Service Hématologie, Hôpital Purpan	Toulouse
France	Service Hématologie Clinique, Hôpital Bretonneau	Tours
France	Service Hématologie - Médecine Interne, Hôpitaux de Brabois	Vandoeuvre-les-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

References & Publications (9)

Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH. Age and acute myeloid leukemia. Blood. 2006 May 1;107(9):3481-5. Epub 2006 Feb 2. — View Citation

Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. — View Citation

Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H, Cordonnier C, Rio B, Gratwohl A, Lange T, Al-Ali H, Storer B, Maloney D, McSweeney P, Chauncey T, Agura E, Bruno B, Maziarz RT, Petersen F, Storb R. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol. 2006 Jan 20;24(3):444-53. Epub 2005 Dec 12. — View Citation

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. — View Citation

Pigneux A, Perreau V, Jourdan E, Vey N, Dastugue N, Huguet F, Sotto JJ, Salmi LR, Ifrah N, Reiffers J. Adding lomustine to idarubicin and cytarabine for induction chemotherapy in older patients with acute myeloid leukemia: the BGMT 95 trial results. Haematologica. 2007 Oct;92(10):1327-34. — View Citation

Sekeres MA, Stone R. Older adults with acute myeloid leukemia. Curr Oncol Rep. 2002 Sep;4(5):403-9. Review. — View Citation

Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P, Lee EJ, Moore JO, Powell BL, Schiffer CA. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med. 1995 Jun 22;332(25):1671-7. — View Citation

Takagi K. [Neurophysiological and clinical aspects of autonomic centers: introduction]. Nihon Seirigaku Zasshi. 1972 May;34(5):257-61. Japanese. — View Citation

Witz F, Sadoun A, Perrin MC, Berthou C, Brière J, Cahn JY, Lioure B, Witz B, François S, Desablens B, Pignon B, Le Prisé PY, Audhuy B, Caillot D, Casassus P, Delain M, Christian B, Tellier Z, Polin V, Hurteloup P, Harousseau JL. A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM). Blood. 1998 Apr 15;91(8):2722-30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		1 year	Yes
Secondary	Complete remission		1 year	Yes
Secondary	Event-free survival		1 year	Yes
Secondary	Prognostic factors		1 year	Yes
Secondary	Quality of Life (QOL)		1 year	Yes