An open label, phase I/II study of Venetoclax in addition to Blinatumomab immunotherapy in adult patients with relapsed/refractory B cell precursor acute lymphoblastic leukemia (BCP-ALL)

Prior treatment

• Treatment with any of the following within 7 days prior to the first dose of study drug: strong cytochrome P450 3A (CYP3A) inhibitors, moderate or strong CYP3A inducers
• Patients with Philadelphia-positive BCP-ALL still receiving TKI
• Prior or concomitant therapy with BH3 mimetics
• Prior therapy with anti CD19 therapy, unless administered in MRD-positive setting (i.e. with bone marrow blasts ≤ 5%)

Other illness

• Current autoimmune disease of any kind or history of autoimmune disease with potential CNS involvement

Other

• Patients with diagnosis of Philadelphia positive BCP-ALL according to WHO classification
• Patients with diagnosis of Burkitt´s Leukemia according to WHO classification
• Patients with extramedullary relapse; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted
• Patients with CNS involvement at relapse (as determined by CSF analysis)
• Patients with suspected or histologically confirmed testicular involvement at relapse

• Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Availability of patient-specific molecular MRD markers of immunoglobulin/T-cell receptor gene rearrangements as assessed with a sensitivity of at least 10E-04
• Diagnosis of Ph-negative, CD19-positive B-precursor acute lymphoblastic leukemia according to WHO classification: − Refractory BCP-ALL to primary induction therapy, including at least three cycles of standard chemotherapy − Untreated first relapse of BCP-ALL with first remission duration < 12 months or − Second or greater relapse of BCP-ALL or refractory relapse or − Relapse of BCP-ALL any time after allogeneic HSCT or
• Positivity of MRD marker of immunoglobulin/T-cell receptor gene rearrangements of greater than 0.01% if in first or second remission of BCP-ALL
• Negative pregnancy test < 7 days before first study drug in women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they fulfil at least one of the following criteria: − Post-menopausal (i.e. 12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml − Post-operative after bilateral ovariectomy with or without hysterectomy − Continuous and correct application of a contraception method with a Pearl index of < 1% (e.g. implants, depots, oral contraceptives, intrauterine device) from initial study drug administration until at least 3 months after the last dose of study drug. A hormonal contraception method must always be combined with a barrier method (e.g. condom) − Sexual abstinence − Vasectomy of the sexual partner
• Ability to understand and willingness to sign a written informed consent
• Willingness to participate in the registry of the German Multicenter Study Group for Adult ALL (GMALL)