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RECRUITINGPhase 2INTERVENTIONAL

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

A Multicentre, Randomized Trial in Adults With de Novo Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia to Assess the Efficacy of Ponatinib Versus Imatinib in Combination With Low-intensity Chemotherapy, to Compare End of Therapy With Indication for SCT Versus TKI, Blinatumomab and Chemotherapy in Optimal Responders and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

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).

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form is available - Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL) Who Should NOT Join This Trial: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

DRUG

Imatinib

Imatinib 600mg QD plus Chemotherapy

DRUG

Ponatinib

Ponatinib 45 mg QD plus chemotherapy

DRUG

Blinatumomab

Patients 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

OTHER

Indication for stem cell transplantation

Patients 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.

Locations (20)

Uniklinik RWTH Aachen
Aachen, Germany
Klinikum Aschaffenburg
Aschaffenburg, Germany
Klinikum Augsburg
Augsburg, Germany
Helios Klinikum Bad Saarow
Bad Saarow, Germany
Klinikum Bayreuth
Bayreuth, Germany
Vivantes Klinikum am Urban
Berlin, Germany
Charité Universitätsmedizin Berlin
Berlin, Germany
Vivantes Klinikum Neukölln
Berlin, Germany
Helios Klinikum Berlin-Buch
Berlin, Germany
Charite Berlin Virchow Klinikum
Berlin, Germany
Evangelisches Krankenhaus Bielefeld
Bielefeld, Germany
UK Knappschaftskrankenhaus Bochum
Bochum, Germany
Evangelische Kliniken Bonn
Bonn, Germany
Universitätsklinikum Bonn
Bonn, Germany
Städtisches Klinikum Braunschweig
Braunschweig, Germany
Klinikum Bremen-Mitte
Bremen, Germany
Klinikum Chemnitz
Chemnitz, Germany
Universitätsklinikum Köln
Cologne, Germany
Klinikum Darmstadt
Darmstadt, Germany
Städtisches Klinikum Dessau
Dessau, Germany