Philadelphia chromosome positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukaemia (ALL) MedDRA version: 21.0 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Blincyto
Product Name: Blincyto
Product Code: AMG103
Pharmaceutical Form: Powder for concentrate for solution for infusion
Trade Name: Iclusig
Product Name: Iclusig
Product Code: PRD4872
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukaemia •Male or female patients > 55 years (biological age) •Not previously treated except with corticosteroids, single dose vincristine or up to three doses of cyclophosphamide (maximum cumulative dose 1g/m2) or intrathecal therapy to control meningeal leukaemia •No uncontrolled CNS involvement •WHO performance status LLN (lower limit of normal) of potassium and magnesium, or corrected to within normal limits with supplements, prior to the first dose of study medication •Signed written inform consent •Molecular evaluation for BCR-ABL1 performed •Willingness of male subjects whose sexual partners are women of child-bearing potential (WOCBP), to use an effective form of contraception (pearl index =65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: •Patient previously treated with tyrosine kinase inhibitors •Known impaired cardiac function (detailed in protocol) •History or presence of clinically relevant CNS pathology (detailed in protocol) •Active ALL in the CNS (confirmed by CSF analysis) or testes (by clinical assessment) •Autoimmune disease with potential CNS involvement •Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C •Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study •Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the Institutional upper limit of normal or > 5 times ULN if considered due to leukemia •Total bilirubin > 1.5 fold the institutional upper limit unless considered to be due to organ involvement •Concurrent severe diseases which exclude the administration of therapy •Chronic pancreatitis or acute pancreatitis as evidenced by clinical symptomatology and/or imaging within 6 months of study entry •Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to compare the molecular response to ponatinib and imatinib in combination with the same induction and consolidation chemotherapy;Secondary Objective: The most important secondary objective is to compare the event free survival with ponatinib and imatinib in combination with the same induction and consolidation chemotherapy. Other considerations are to compare, the safety and tolerability of the drugs being investigated, the molecular response to the therapies, the overall survival and relapse-free survival and to measure and compare the activity of the therapies in the laboratory.;Primary end point(s): Achievement of a molecular response defined by a BCR-ABL1/ABL1 (B/A) transcript ratio of =10-4 by the time point for MRD assessment after consolidation 2 or within 5 months after start of study treatment, whichever is earlier in arms 1 and 2 ;Timepoint(s) of evaluation of this end point: After consolidation course 2 for arms 1 and 2 of the trial, or within 5 months after start of study treatment, whichever is earlier. This takes into account substantial treatment delays or termination of study treatment prior to consolidation cycle 2 in the two chemotherapy-containing treatment arms. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To compare the event free survival with ponatinib and imatinib in combination with the same induction and consolidation chemotherapy. 2. To compare the molecular response to induction and consolidation therapy with ponatinib in combination with either chemotherapy or with blinatumomab 3. To compare the safety and tolerability of ponatinib and imatinib in combination with induction and consolidation chemotherapy 4. To compare the efficacy of ponatinib and imatinib in combination with induction and consolidation chemotherapy as determined by overall survival and relapse-free survival 5. To determine the frequency of BCR-ABL1 tyrosine kinase domain mutations on therapy (T315I, p-loop and compound mutations) by standard molecular genetic techniques;Timepoint(s) of evaluation of this end point: 1. Events will be recorded in all patients 2. Time to best molecular response (from start of treatment) in all patients 3. Adverse event grades 3 to 5 will be collected throughout IMP treatment 4. Relapse free survival, and overall survival - survival measured from trial entry until death 5. Detection of a T315I or p-loop mutation, or detection of a compound mutation, at any time during trial treatment and follow-up | — |
Countries
Finland, France, Sweden, United Kingdom
Contacts
Public ContactMorisset
CH de Versailles
Outcome results
None listed