Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

• Status: Recruiting
• Trial end date: 2029-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Goethe University
• Collaborators: Deutsche Leukämie- & Lymphom-Hilfe; German Federal Ministry of Education and Research
• Treatments: Blinatumomab; Imatinib Mesylate; Ponatinib

Criteria

Inclusion Criteria:

• 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

• Signed written inform consent

• Molecular evaluation for BCR-ABL1 performed

• Negative pregnancy test in women of childbearing potential

• Woman of childbearing potential willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment (Pearl-Index <1%). Male who has a female partner of childbearing potential willing to use 2 highly effective forms of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment (Pearl-Index <1%).

• Normal serum levels > 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

• Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis

• Normal QTcF interval ≤450 ms for males and ≤470 ms for females

• Signed and dated written informed consent is available

• Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Exclusion Criteria:

• 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

• Known impaired cardiac function, including any of the following: as detailed in protocol

• Symptomatic peripheral vascular disease

• Any history of ischemic stroke or transient ischemic attacks (TIAs)

• Uncontrolled hypertriglyceridaemia

• History or presence of clinically relevant CNS pathology as detailed in protocol

• History or active relevant autoimmune disease

• Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation

• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C

• History of pancreatitis within 6 months previous to start of treatment within the trial

• 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 by the leukemia or to M. Gilbert / M. Meulengracht

• Concurrent severe diseases which exclude the administration of therapy e.g. severe, uncontrolled acute or chronic infections

• Inability to understand and/or unwillingness to sign a written informed consent