Comparing treatments for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

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)

This study tests whether Ponatinib or Imatinib, both with low-dose chemotherapy, can help adults with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia feel better, and looks at how Blinatumomab can be used for those who respond well or not to these treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Goethe University (Academic / other)
• Drugs / interventions: Rituximab, Blinatumomab, Imatinib, Ponatinib, chemotherapy, cyclophosphamide
• Locations: 85 sites (Aachen and 84 other locations)
• Trial ID: NCT06061094 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of Ponatinib versus Imatinib, both combined with low-dose chemotherapy, in treating adults with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL). It also investigates the continuation of therapy with Blinatumomab for patients who respond well to treatment and the use of Blinatumomab for those who do not respond adequately. The study aims to optimize treatment strategies and improve outcomes for patients with this aggressive form of leukemia.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 who have been diagnosed with Philadelphia chromosome or BCR-ABL1 positive ALL and have not received prior treatment.

Not a fit: Patients who have previously undergone extensive treatment for Ph+ ALL or have an ECOG performance status greater than 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment protocols that enhance survival rates and quality of life for patients with Ph+ ALL.

How similar studies have performed: Other studies have shown promise in using targeted therapies like Blinatumomab and tyrosine kinase inhibitors for Ph+ ALL, suggesting that this approach may yield beneficial results.

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

Where this trial is running

Aachen and 84 other locations

• Uniklinik RWTH Aachen — Aachen, Germany (Recruiting)
• Klinikum Aschaffenburg — Aschaffenburg, Germany (Recruiting)
• Klinikum Augsburg — Augsburg, Germany (Recruiting)
• Helios Klinikum Bad Saarow — Bad Saarow, Germany (Recruiting)
• Klinikum Bayreuth — Bayreuth, Germany (Recruiting)
• Vivantes Klinikum am Urban — Berlin, Germany (Recruiting)
• Charité Universitätsmedizin Berlin — Berlin, Germany (Recruiting)
• Vivantes Klinikum Neukölln — Berlin, Germany (Recruiting)
• Helios Klinikum Berlin-Buch — Berlin, Germany (Recruiting)
• Charite Berlin Virchow Klinikum — Berlin, Germany (Recruiting)
• Evangelisches Krankenhaus Bielefeld — Bielefeld, Germany (Recruiting)
• UK Knappschaftskrankenhaus Bochum — Bochum, Germany (Recruiting)
• Evangelische Kliniken Bonn — Bonn, Germany (Recruiting)
• Universitätsklinikum Bonn — Bonn, Germany (Recruiting)
• Städtisches Klinikum Braunschweig — Braunschweig, Germany (Recruiting)
• Klinikum Bremen-Mitte — Bremen, Germany (Recruiting)
• Klinikum Chemnitz — Chemnitz, Germany (Recruiting)
• Universitätsklinikum Köln — Cologne, Germany (Recruiting)
• Klinikum Darmstadt — Darmstadt, Germany (Recruiting)
• Städtisches Klinikum Dessau — Dessau, Germany (Recruiting)
• Klinikum Dortmund — Dortmund, Germany (Recruiting)
• St. Johannes Hospital Dortmund — Dortmund, Germany (Recruiting)
• Universitätsklinikum Carl Gustav Carus Dresden — Dresden, Germany (Recruiting)
• Helios Klinikum Duisburg — Duisburg, Germany (Recruiting)
• Universitätsklinikum Düsseldorf — Düsseldorf, Germany (Recruiting)
• Marien Hospital Düsseldorf — Düsseldorf, Germany (Recruiting)
• Universitätsklinikum Erlangen — Erlangen, Germany (Recruiting)
• St.-Antonius-Hospital — Eschweiler, Germany (Recruiting)
• Universitätsklinikum Essen — Essen, Germany (Recruiting)
• Evangelisches Krankenhaus Essen-Werden — Essen, Germany (Recruiting)
• Department of Medicine, Hematology and Oncology, Goethe University Hospital Frankfurt — Frankfurt, Germany (Recruiting)
• Universitätsklinikum Freiburg — Freiburg im Breisgau, Germany (Recruiting)
• Niels-Stensen-Kliniken Georgsmarienhütte — Georgsmarienhütte, Germany (Recruiting)
• Wilhelm-Anton-Hospital — Goch, Germany (Recruiting)
• Universitätsmedizin Göttingen — Göttingen, Germany (Recruiting)
• Universitätsmedizin Greifswald — Greifswald, Germany (Recruiting)
• Klinikum Gütersloh — Gütersloh, Germany (Recruiting)
• Katholisches Krankenhaus Hagen — Hagen, Germany (Recruiting)
• Universitätsklinikum Halle — Halle, Germany (Recruiting)
• Asklepios Klinik St. Georg Hamburg — Hamburg, Germany (Not_yet_recruiting)
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (Recruiting)
• Medizinische Hochschule Hannover — Hanover, Germany (Recruiting)
• Universitätsklinikum Heidelberg — Heidelberg, Germany (Recruiting)
• Marien Hospital Herne — Herne, Germany (Recruiting)
• Universitätsklinikum des Saarlandes — Homburg, Germany (Recruiting)
• Klinikum Idar-Oberstein — Idar-Oberstein, Germany (Recruiting)
• Universitätsklinikum Jena — Jena, Germany (Recruiting)
• Städtisches Klinikum Karlsruhe — Karlsruhe, Germany (Recruiting)
• St. Vincentius-Kliniken Karlsruhe — Karlsruhe, Germany (Recruiting)
• Klinikum Kassel — Kassel, Germany (Recruiting)

Study contacts

• Principal investigator: Nicola Goekbuget, MD — Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
• Study coordinator: Nicola Goekbuget, MD

Conditions Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia; Tyrosinekinase Inhibitors; Blinatumomab