Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorGoethe University
About this trial
The current Standard of Care (SoC) in younger patients with Ph+ ALL is Imatinib in combination with low-dose chemotherapy, change of TKI in case of persistent MRD above 10-3 after consolidation I and indication for stem cell transplantation.
The EVOLVE trial aims to answer three questions challenging the current SoC:
Use of Ponatinib compared to Imatinib both in combination with low-dose chemotherapy and consolidation I (randomization I).
In MRD good responders: Omit end of therapy in primary care and indication for SCT but continue therapy with TKI, chemotherapy and Blinatumomab as additional antileukemic compound (randomization II).
In MRD poor responders: Omit indication for TKI change but give instead Blinatumomab followed by end of therapy in primary care and indication for SCT (non-randomized).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male or female patients >= 18 years, <=65 years
Philadelphia chromosome or BCR-ABL1 positive ALL
Not previously treated except with corticosteroids ≤ 7 days, standard GMALL prephase with dexamethasone and cyclophosphamide including intrathecal therapy, hydroxyurea, a single dose vincristine or other cytostatic drugs and start of standard induction for Ph-positive ALL (1 dose vincristine, 1 dose of Rituximab, 2 doses dexamethasone and up to 5 days Imatinib)
ECOG performance status ≤2
Disqualifiers
History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of protocol-specified therapy with defined exceptions
Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab
Patient previously treated with tyrosine kinase inhibitors
Nursing women
Trial design
Design model
Parallel
Treatments tested in this trial
Imatinib
DrugImatinib 600mg QD plus Chemotherapy
Ponatinib
DrugPonatinib 45 mg QD plus chemotherapy
Blinatumomab
DrugPatients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy
Indication for stem cell transplantation
Other interventionPatients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.
Treatment groups
220 Participants
are divided into 5 treatment groupsGroup A: A: Imatinib + low dose chemotherapyActive comparator 1 intervention
Group B: B: Ponatinib + low dose chemotherapyExperimental treatment 1 intervention
Group C: C: Molecular CR: End of therapy with indication for SCTActive comparator 1 intervention
Group D: D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and BlinatumomabExperimental treatment 3 interventions
Group E: E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of BlinaExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care)
Probability of overall survival up to 4 years from randomization I in patients with mo-lecular remission after consolidation 1 comparing a combination treatment of TKI, Blina-tumomab and chemotherapy versus EOT with indication for SCT
Time frame
up to 4 years from randomization ISecondary outcomes
1
Rate of molecular complete remission at week 11 after consolidation
Rate of molecular complete remission at week 11 after consolidation with chemotherapy in combination with Ponatinb versus Imatinib
Time frame
week 11 after consolidationOther outcomes
1
Probability of remission duration
Probability of remission duration
Time frame
at 2 years, 3 years, 4 yrs2
Cumulative incidence of relapse
Cumulative incidence of relapse
Time frame
at 2 years, 3 years, 4 yrs3
Mortality in CR
Mortality in CR
Time frame
at 2 years, 3 years, 4 yrs4
Probability of relapse-free survival
Probability relapse-free survival
Time frame
at 2 years, 3 years, 4 yrsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Goethe University
Lead sponsor
Deutsche Leukämie- & Lymphom-Hilfe
Collaborator
German Federal Ministry of Education and Research
Collaborator
Source ClinicalTrials.gov