Clinical trial NCT00327678: Treatment of Acute Lymphoblastic Leukemia (ALL) in Younger Adults
Official title: Young Adult With Acute Lymphoblastic Leukemia (ALL) : a Multicentric Protocol. GRAALL 2005 : T ALL or B ALL Non Ph GRAALL 2005 R : B ALL Non Ph CD20+ GRAAPH 2005 : ALL Ph
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia, Lymphocytic
Keywords: ALL,
young patients,
chemotherapy,
Mabtera,
Imatinib,
allogeneic transplant
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Group for Research in Adult Acute Lymphoblastic Leukemia
First posted: 2006-05-18
Enrollment: 1080
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicenter trial of treatment for young ALL patients. All ALL patients will receive the same steroid pre-phase in order to evaluate sensitivity or resistance. Then, patients will be included into 3 specific trials according to biological features (immunophenotype, cytogenetics, and molecular biology).

Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) 2005:

* T ALL or B ALL non Ph (N=810 patients planned).
* GRAALL 2005 R: B ALL non Ph CD20+ (N=220 patients planned).
* GRAAPH 2005: ALL Ph+ (N=270 patients planned)

Detailed description: GRAALL 2005: T ALL or B ALL non Ph

Randomization between standard versus intensified cyclophosphamide administration during a 4-drug, 4 week chemotherapy and late intensification.

(N=810 patients planned)

GRAALL 2005 R: B ALL non Ph CD20+

Randomization between standard versus intensified cyclophosphamide administration during a 4-drug, 4 week chemotherapy and late intensification.

Randomization between Mabthera (rituximab) or no Mabthera during all induction and consolidation courses.(N=220 patients planned)

Allogenic transplantation will be performed depending on unfavourable risk factors.

GRAAPH 2005: ALL Ph

Randomization between an imatinib-based induction and a chemotherapy + imatinib induction. (N=270 patients planned)

Allogenic transplantation will be systematically performed in the presence of related or unrelated donors.

Autologous transplantation could be performed in the absence of a donor in case of Molecular Residual Disease (MRD) ≤ 10-4.

Consolidation therapy will be performed in the absence of a donor in case of MRD \> 10-4.

Eligibility criteria: Inclusion Criteria:

* 18-59 years
* ALL newly diagnosed (blast \< 20%)
* Central Nervous System (CNS) positive or negative
* Signed written informed consent
* For GRAAPH trial only: t(9;22) or BCR- ABL positive

Exclusion Criteria:

* Lymphoblastic lymphoma
* ALL 3
* Chronic myeloid leukemia
* Severe organ condition

Primary outcomes:
measure: Event free survival for all patients
timeFrame: January 2014
measure: GRAAPH: Percentage of patients with minimum residual disease (MRD) < 10-4 after induction and/or consolidation (= salvage)
timeFrame: January 2014
Secondary outcomes:
measure: CR in 1 or 2 courses
timeFrame: January 2014
measure: Death in induction
timeFrame: January 2014
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: January 2014
measure: Death in first CR
timeFrame: January 2014
measure: Relapse
timeFrame: January 2014
measure: Relapse free survival
timeFrame: January 2014
measure: Overall Survival
timeFrame: January 2014
Other outcomes:
Locations:
city: Lyon
country: France
facility: Group for Research in Adult Acute Lymphoblastic Leukemia - GRAALL -
Study officials:
affiliation: GRAALL Group
name: HERVE DOMBRET, MD, PHD
role: STUDY_CHAIR
References:
citation: Orvain C, Balsat M, Tavernier E, Marolleau JP, Pabst T, Chevallier P, de Gunzburg N, Cacheux V, Huguet F, Chantepie S, Caillot D, Chalandon Y, Frayfer J, Bonmati C, Lheritier V, Ifrah N, Dombret H, Boissel N, Hunault-Berger M. Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study. Blood. 2020 Jul 16;136(3):328-338. doi: 10.1182/blood.2020004919.
citation: 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.
citation: Bond J, Touzart A, Lepretre S, Graux C, Bargetzi M, Lhermitte L, Hypolite G, Leguay T, Hicheri Y, Guillerm G, Bilger K, Lheritier 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.
citation: Huguet F, Chevret S, Leguay T, Thomas X, Boissel N, Escoffre-Barbe M, Chevallier P, Hunault M, Vey N, Bonmati C, Lepretre S, Marolleau JP, Pabst T, Rousselot P, Buzyn A, Cahn JY, Lheritier V, Bene MC, Asnafi V, Delabesse E, Macintyre E, Chalandon Y, Ifrah N, Dombret H; Group of Research on Adult ALL (GRAALL). Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial. J Clin Oncol. 2018 Aug 20;36(24):2514-2523. doi: 10.1200/JCO.2017.76.8192. Epub 2018 Jun 4.
citation: Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, Chevallier P, Hunault M, Boissel N, Escoffre-Barbe M, Hess U, Vey N, Pignon JM, Braun T, Marolleau JP, Cahn JY, Chalandon Y, Lheritier V, Beldjord K, Bene MC, Ifrah N, Dombret H; for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.
citation: 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.
citation: Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, Raffoux E, Leguay T, Rousselot P, Lepretre S, Escoffre-Barbe M, Maury S, Berthon C, Tavernier E, Lambert JF, Lafage-Pochitaloff M, Lheritier V, Chevret S, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015 Jun 11;125(24):3711-9. doi: 10.1182/blood-2015-02-627935. Epub 2015 Apr 15.
citation: Chien WW, Catallo R, Chebel A, Baranger L, Thomas X, Bene 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.
citation: Dhedin 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, Lheritier 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.
citation: 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, Cave H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lheritier V, Bene 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.
citation: Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengline E, De Gunzburg N, Payet-Bornet D, Lhermitte L, Mossafa H, Lheritier 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.
citation: Ben Abdelali R, Asnafi V, Petit A, Micol JB, Callens C, Villarese P, Delabesse E, Reman O, Lepretre S, Cahn JY, Guillerm G, Berthon C, Gardin C, Corront B, Leguay T, Bene MC, Ifrah N, Leverger G, Dombret H, Macintyre E. The prognosis of CALM-AF10-positive adult T-cell acute lymphoblastic leukemias depends on the stage of maturation arrest. Haematologica. 2013 Nov;98(11):1711-7. doi: 10.3324/haematol.2013.086082. Epub 2013 Jul 5.