Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children (ESPHALL)

• ClinicalTrials.gov Identifier: NCT00287105
• Recruitment Status: Completed
• First Posted: February 6, 2006
• Last Update Posted: October 20, 2017
• Sponsor: Rennes University Hospital
• Collaborators: Ministry of Health, France; Novartis
• Information provided by (Responsible Party): Rennes University Hospital

Tracking Information

• First Submitted Date: February 3, 2006
• First Posted Date: February 6, 2006
• Last Update Posted Date: October 20, 2017
• Actual Study Start Date: December 2005
• Actual Primary Completion Date: March 30, 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 17, 2012): Disease free survival (DFS). DFS will be calculated as the time from inclusion to either one of the following events: relapse, death in CCR, second malignancies. [ Time Frame: 2 years ]
• Original Primary Outcome Measures (submitted: February 3, 2006): Disease Free Survival : time from randomization to relapse, death in complete remission (CR), second malignancies

Current Secondary Outcome Measures (submitted: September 17, 2012)

• Compare long term outcome between patients treated by BFM-chemotherapy and patient undergoing more intensive chemotherapy (protocole COGAALL0031 : Children Oncology Group-USA). [ Time Frame: 2 years ]
• Long-term clinical outcome : Disease free survival (DFS), Event-Free Survival (EFS) and Overall Survival (OS) in each risk groups. [ Time Frame: 2 years ]
• Pattern of molecular response (MRD) [ Time Frame: 5 time points between S4 and S22 ]
• Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group. [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: February 3, 2006)

• - To Determine the safety and feasibility of Imatinib added to chemotherapy,
• - To Evaluate the long-term clinical outcome (EFS, survival) in both groups,
• - To Assess the antileukemic potential of Imatinib by analyzing the pattern by arm of the molecular response on the basis of 5 measurements of minimal residual disease (MRD) taken at 5 time points between S4 and S22,
• - To evaluate the role of molecular response as surrogate for DFS.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children
• Official Title: An Open-label, Phase II Study to Explore the Safety and Efficacy of Imatinib With Chemotherapy in Pediatric Patients With Ph+ / BCR-ABL+ Acute Lymphoblastic Leukemia (Ph+ALL)
• Brief Summary: The purpose of this study is to determine whether Imatinib is safe and effective in association with intensive treatment of Ph+ALL in children.
• Detailed Description: Recent advances in treatment have increased the cure of childhood ALL to 75% or better. However, attempts to improve results for resistant subtypes of ALL, such as Ph+ ALL, have been largely unsuccessful. Imatinib, an inhibitor of protein-tyrosine kinases, is currently being tested in several phase I, II and III trials covering most Chronic Myeloid Leukemia patient populations and patients with overtly relapsed or refractory Ph+ALL. Pediatric patients with Ph+ALL will receive Imatinib, added to intensive, post-induction BFM-type chemotherapy. The endpoint will be the evaluation on the long-term clinical outcome, in particular on the Disease Free Survival (DFS).
• 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
• Philadelphia Chromosome

Intervention

Drug: Standard chemotherapy + Imatinib

Patients receive Imatinib together with the standard chemotherapy regimen of phase IB and after each of three consecutive blocks of the standard chemotherapy in the consolidation phase

Other Names:

• Glivec
• Gleevec

Study Arms

• Good risk Ph+ALL
  For protocols which adopt a steroid prephase: patients who are Prednisone-good responder and achieve CR after the induction course. For protocols which do not adopt steroid prephase: patients who have M1/M2 BM at day 15 or M1 BM at day 21 and achieve CR after the induction course. Expected stratification in this group: 70-75%.
  Intervention: Drug: Standard chemotherapy + Imatinib
• Poor risk Ph+ALL
  For protocols which adopt a steroid prephase: patients who are Prednisone poor-responders. For protocol which do not adopt a steroid prephase: patients who have M3 BM at day 15 or M2/M3 BM at day 21. For all protocols: patients who do not achieve CR after the induction course. Expected stratification: 25-30%.
  Intervention: Drug: Standard chemotherapy + Imatinib

Publications *

• Tasian SK, Peters C. Targeted therapy or transplantation for paediatric ABL-class Ph-like acute lymphocytic leukaemia? Lancet Haematol. 2020 Dec;7(12):e858-e859. doi: 10.1016/S2352-3026(20)30369-0.
• Biondi A, Gandemer V, De Lorenzo P, Cario G, Campbell M, Castor A, Pieters R, Baruchel A, Vora A, Leoni V, Stary J, Escherich G, Li CK, Cazzaniga G, Cavé H, Bradtke J, Conter V, Saha V, Schrappe M, Grazia Valsecchi M. Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial. Lancet Haematol. 2018 Dec;5(12):e641-e652. doi: 10.1016/S2352-3026(18)30173-X.
• Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. doi: 10.1016/S1470-2045(12)70377-7. Epub 2012 Aug 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 14, 2017): 49
• Original Enrollment (submitted: February 3, 2006): 40
• Actual Study Completion Date: March 3, 2017
• Actual Primary Completion Date: March 30, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Children and adolescents aged 1 to 17 years at diagnostic
• Documented Ph+ ALL
• Eligibility for the current local prospective therapeutic study of childhood ALL
• Informed consent given by the parents or by legal guardian

Exclusion Criteria:

• Abnormal hepatic functions
• Abnormal renal functions
• Active systemic bacterial, fungal or viral infection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 18 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: NCT00287105
• Other Study ID Numbers: EUDRACT 2004-001647-30; PHRC/04-04; CIC0203/043
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Rennes University Hospital
• Study Sponsor: Rennes University Hospital

Collaborators

• Ministry of Health, France
• Novartis

Investigators

• Study Director: Andrea Biondi, MD; Ospedale S. Gerardo - Monza
• Principal Investigator: Virginie Gandemer, MD; Rennes University Hospital

• PRS Account: Rennes University Hospital
• Verification Date: February 2017