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

Launched by GOETHE UNIVERSITY · Sep 24, 2023

Keywords

ClinConnect Summary

The EVOLVE trial is a research study looking at new ways to treat adults with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL), a type of blood cancer. The trial is comparing different treatments to see if they can improve outcomes for patients. Specifically, it will compare two medications, Imatinib and Ponatinib, both used with low-dose chemotherapy. It will also explore whether certain patients can skip some therapies or switch to different treatments based on their response to initial therapy.

To participate in this trial, you must be between 18 and 65 years old and have not received extensive treatment for your leukemia, except for minor medications. You will need to provide consent to join and undergo health evaluations. If you qualify, you can expect to receive a combination of medicines, and your progress will be closely monitored. It's important to know that the trial is currently recruiting participants, and the goal is to find the best treatments to help improve survival and quality of life for those living with this condition.

Gender

ALL

Eligibility 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