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

NCT ID: NCT00590837

Last Updated: 2014-04-02

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

459 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2013-12-31

Brief Summary

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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.

Detailed Description

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* 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

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Patients will be treated by adding lomustine to chemotherapy

Group Type EXPERIMENTAL

Lomustine

Intervention Type DRUG

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.

2

Patients will be treated without adding lomustine to chemotherapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arnaud Pigneux, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Bordeaux, France

Locations

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Services maladies du sang, cancérologie, Hôpital Sud, CHU Amiens

Amiens, , France

Site Status

Service des maladies du sang, Centre Hospitalier Universitaire d'Angers

Angers, , France

Site Status

Service Hématologie, Centre Hospitalier Annecy

Annecy, , France

Site Status

C.H Victor Dupouy

Argenteuil, , France

Site Status

Service Médecine Interne, Onco-Hématologie, Maladies Infectieuses, Hôpital Henri Duffaut, Centre Hospitalier Avignon

Avignon, , France

Site Status

Service Hématologie, Centre Hospitalier de la Côte Basque

Bayonne, , France

Site Status

Service Hématologie, Hôpital Minjoz

Besançon, , France

Site Status

Unité Hématologie, Centre Hospitalier Blois

Blois, , France

Site Status

Service des maladies du sang - Hôpital Haut-Lévêque

Bordeaux - Pessac, , France

Site Status

Service Hématologie, Hôpital Dr Duchenne

Boulogne-sur-Mer, , France

Site Status

Service Hématologie, Hôpital Augustin Morvan

Brest, , France

Site Status

Service Hématologie et Thérapie cellulaire, Pavillon Villemin Pasteur, CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Service Oncologie - Hématologie, Hôpital Pasteur, Centre Hospitalier Colmar

Colmar, , France

Site Status

Service Hématologie Clinique, CHU Dijon Hôpital des enfants

Dijon, , France

Site Status

Service Hématologie Clinique, Hôpital Michallon, CHU de Grenoble

Grenoble, , France

Site Status

Service Onco-Hématologie 3, Institut Paoli Calmettes

Marseille, , France

Site Status

Service Hématologie Oncologie, CHR Metz-Thionville

Metz, , France

Site Status

Service Hématologie Oncologie, Hôpital Lapeyronie, CHU de Montpellier

Montpellier, , France

Site Status

Département d'hématologie, Hôpital E.Muller, Centre Hospitalier de Mulhouse

Mulhouse, , France

Site Status

Service Hématologie Clinique, CHU -Hôtel Dieu

Nantes, , France

Site Status

Service Hématologie Clinique, Hôpital Archet 1

Nice, , France

Site Status

Service Médecine B - Unité Onco-hématologique, CHU Caremeau

Nîmes, , France

Site Status

Service Oncologie Médicale, Hôpital de la Source

Orléans, , France

Site Status

Unité d'Hématologie, Hôpital Cochin

Paris, , France

Site Status

Service Hématologie, CHG Saint Jean

Perpignan, , France

Site Status

Service Hématologie Clinique, Hôpital Robert Debre

Reims, , France

Site Status

Service Hématologie Clinique, Hôpital Pontchaillou

Rennes, , France

Site Status

Service d'Hématologie, Institut de Cancérologhie de la Loire

Saint Priez En Jarez, , France

Site Status

Département d'Hématologie et d'Oncologie, Hôpital CHRU de Hautepierre

Strasbourg, , France

Site Status

Service Hématologie, Hôpital Purpan

Toulouse, , France

Site Status

Service Hématologie Clinique, Hôpital Bretonneau

Tours, , France

Site Status

Service Hématologie - Médecine Interne, Hôpitaux de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

References

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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. doi: 10.1182/blood-2005-09-3724. Epub 2006 Feb 2.

Reference Type BACKGROUND
PMID: 16455952 (View on PubMed)

Sekeres MA, Stone R. Older adults with acute myeloid leukemia. Curr Oncol Rep. 2002 Sep;4(5):403-9. doi: 10.1007/s11912-002-0034-y.

Reference Type BACKGROUND
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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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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. doi: 10.1056/NEJM199506223322503.

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PMID: 7760868 (View on PubMed)

Witz F, Sadoun A, Perrin MC, Berthou C, Briere J, Cahn JY, Lioure B, Witz B, Francois S, Desablens B, Pignon B, Le Prise 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 Leucemies Aigues Myeloblastiques (GOELAM). Blood. 1998 Apr 15;91(8):2722-30.

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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. doi: 10.3324/haematol.11068.

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Takagi K. [Neurophysiological and clinical aspects of autonomic centers: introduction]. Nihon Seirigaku Zasshi. 1972 May;34(5):257-61. No abstract available. Japanese.

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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. doi: 10.1182/blood-2007-02-069666. Epub 2007 Mar 6.

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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. doi: 10.1200/JCO.2005.03.1765. Epub 2005 Dec 12.

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Largeaud L, Cornillet-Lefebvre P, Hamel JF, Dumas PY, Prade N, Dufrechou S, Plenecassagnes J, Luquet I, Blanchet O, Banos A, Bene MC, Bernard M, Bertoli S, Bonmati C, Fornecker LM, Guieze R, Haddaoui L, Hunault M, Ianotto JC, Jourdan E, Ojeda M, Peterlin P, Vey N, Zerazhi H, Yosr H, Mineur A, Cahn JY, Ifrah N, Recher C, Pigneux A, Delabesse E; French Innovative Leukemia Organization (FILO). Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study. Leukemia. 2021 May;35(5):1291-1300. doi: 10.1038/s41375-020-01031-1. Epub 2020 Sep 18.

Reference Type DERIVED
PMID: 32943750 (View on PubMed)

Other Identifiers

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CHUBX 2007/13

Identifier Type: -

Identifier Source: org_study_id

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