Feasibility of Risk-Adapted Therapy in Young Adult Acute Lymphoblastic Leukemia: a Multicenter Trial (GRAALL2003)

• ClinicalTrials.gov Identifier: NCT00222027
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: January 7, 2009
• Sponsor: University Hospital, Toulouse
• Collaborator: Ministry of Health, France
• Information provided by: University Hospital, Toulouse

Tracking Information

• First Submitted Date: September 13, 2005
• First Posted Date: September 22, 2005
• Last Update Posted Date: January 7, 2009
• Study Start Date: November 2003
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 13, 2005): Hierarchical evaluation of baseline poor-prognosis factors and response to initial therapy in younger adults with ALL
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: September 13, 2005): Hematologic and non hematologic toxicity of induction, consolidation and late intensification.
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Feasibility of Risk-Adapted Therapy in Young Adult Acute Lymphoblastic Leukemia: a Multicenter Trial
• Official Title: GRAALL 2003 Trial (ALL 15-59 Years). Feasibility of Risk-Adapted Therapy in Young Adult Acute Lymphoblastic Leukemia: a Multicenter Trial
• Brief Summary: Several prognostic predictors, including baseline ALL features and response to initial therapy, have been described in adult ALL raising the issue of whether these predictors might be redundant and which must be considered for treatment stratification. In the GRAALL-2003 prospective Phase 2 study, we aim to hierarchize the following high-risk factors in Ph-negative ALL patients.
• Detailed Description: 1) baseline (BL) : WBC30G/L in B-lineage, CNS involvement, MLL-AF4 and E2A-PBX fusions, haploidy/near-triploidy; 2) early response (ER) : corticoresistance after prophase (CsR), chemoresistance at Day 8 (ChR); all CsR and/or ChR patients are planned to receive higher doses of cyclophosphamide (HyperC) at Day 15 of induction; 3) induction response (IR) : no CR or Ig-TCR minimal residual disease (MRD) 10-2 after standard or HyperC induction. Allogeneic stem cell transplantation is proposed to patients with a donor and at least one BL, ER, or IR factor.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Lymphoblastic Leukemia
• Intervention: Procedure: Collection of treatment-stratefying prognostic factors
• Study Arms: Not Provided

Publications *

• Touzart A, Boissel N, Belhocine M, Smith C, Graux C, Latiri M, Lhermitte L, Mathieu EL, Huguet F, Lamant L, Ferrier P, Ifrah N, Macintyre E, Dombret H, Asnafi V, Spicuglia S. Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia. Haematologica. 2020 Jun;105(6):1575-1581. doi: 10.3324/haematol.2019.223677. Epub 2019 Sep 19.
• Bond J, Touzart A, Leprêtre S, Graux C, Bargetzi M, Lhermitte L, Hypolite G, Leguay T, Hicheri Y, Guillerm G, Bilger K, Lhéritier V, Hunault M, Huguet F, Chalandon Y, Ifrah N, Macintyre E, Dombret H, Asnafi V, Boissel N. DNMT3A mutation is associated with increased age and adverse outcome in adult T-cell acute lymphoblastic leukemia. Haematologica. 2019 Aug;104(8):1617-1625. doi: 10.3324/haematol.2018.197848. Epub 2019 Jan 17.
• Bond J, Marchand T, Touzart A, Cieslak A, Trinquand A, Sutton L, Radford-Weiss I, Lhermitte L, Spicuglia S, Dombret H, Macintyre E, Ifrah N, Hamel JF, Asnafi V. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. Haematologica. 2016 Jun;101(6):732-40. doi: 10.3324/haematol.2015.141218. Epub 2016 Mar 4.
• Chien WW, Catallo R, Chebel A, Baranger L, Thomas X, Béné MC, Gerland LM, Schmidt A, Beldjord K, Klein N, Escoffre-Barbe M, Leguay T, Huguet F, Larosa F, Hayette S, Plesa A, Ifrah N, Dombret H, Salles G, Chassevent A, Ffrench M. The p16(INK4A)/pRb pathway and telomerase activity define a subgroup of Ph+ adult Acute Lymphoblastic Leukemia associated with inferior outcome. Leuk Res. 2015 Apr;39(4):453-61. doi: 10.1016/j.leukres.2015.01.008. Epub 2015 Jan 25.
• Dhédin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, Thomas X, Chevallier P, Nguyen S, Coiteux V, Bourhis JH, Hichri Y, Escoffre-Barbe M, Reman O, Graux C, Chalandon Y, Blaise D, Schanz U, Lhéritier V, Cahn JY, Dombret H, Ifrah N; GRAALL group. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015 Apr 16;125(16):2486-96; quiz 2586. doi: 10.1182/blood-2014-09-599894. Epub 2015 Jan 13.
• Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cavé H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lhéritier V, Béné MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014 Jun 12;123(24):3739-49. doi: 10.1182/blood-2014-01-547695. Epub 2014 Apr 16.
• Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengliné E, De Gunzburg N, Payet-Bornet D, Lhermitte L, Mossafa H, Lhéritier V, Bond J, Huguet F, Buzyn A, Leguay T, Cahn JY, Thomas X, Chalandon Y, Delannoy A, Bonmati C, Maury S, Nadel B, Macintyre E, Ifrah N, Dombret H, Asnafi V. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol. 2013 Dec 1;31(34):4333-42. doi: 10.1200/JCO.2012.48.5292. Epub 2013 Oct 28.
• Maury S, Huguet F, Leguay T, Lacombe F, Maynadié M, Girard S, de Labarthe A, Kuhlein E, Raffoux E, Thomas X, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Rousselot P, Macintyre E, Ifrah N, Dombret H, Béné MC; Group for Research on Adult Acute Lymphoblastic Leukemia. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica. 2010 Feb;95(2):324-8. doi: 10.3324/haematol.2009.010306. Epub 2009 Sep 22.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: September 13, 2005): 300
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2008
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 15-59 years
• acute lymphoblastic leukemia newly diagnosed
• signed written informed consent

Exclusion Criteria:

• Lymphoblastic lymphoma
• Acute lymphoblastic leukemia 3
• Chronic Myeloid Leukemia acutisation
• Sever organ condition

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years to 59 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00222027
• Other Study ID Numbers: 0200701; PHRC
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: LLAU Marie-Elise, University Hospital Toulouse
• Study Sponsor: University Hospital, Toulouse
• Collaborators: Ministry of Health, France

Investigators

• Principal Investigator: Françoise HUGUET-RIGAL, MD; University Hospital, Toulouse

• PRS Account: University Hospital, Toulouse
• Verification Date: January 2009