Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL+ B-ALL

Prior treatment

• Any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
• Prior hematologic malignancy and/or alloSCT; this includes known CML
• Concurrent or prior (within 30 days) treatment with another investigational agent or study drug
• Female subject is pregnant or breastfeeding or planning to become pregnant breastfeed during treatment, and for an additional 4 months after the last dose of protocol-specified therapy

Other illness

• Uncontrolled infection
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus
• Presence of cardiovascular disease of clinical relevance within the past 3 months. This includes:
  • 5.2.3.1 Unstable angina 5.2.3.2 Myocardial infarction 5.2.3.3 Transient ischemic attack or stroke 5.2.3.4 Peripheral vascular infarction, claudication and/or revascularization 5.2.3.5 Symptomatic congestive heart failure 5.2.3.6 Clinically significant significant atrial/ventricular tachyarrhythmias 5.2.3.7 Venous thromboembolic event requiring systemic anticoagulation
  • Please consult the sponsor if there are specific concerns outside of these criteria
• Uncontrolled hypertension
• History or presence of clinically relevant CNS pathology or event.
  • This may include, for example:
  • epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis.
  • Before excluding a potential subject, please consult the sponsor.
• History of malignancy other than ALL within 3 years prior to start of protocol-specified therapy except for:
  • malignancy treated with curative intent and with no known active disease present for 3 years before enrollment, and felt to be at low risk for recurrence by the treating physician
  • adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • adequately treated cervical carcinoma in situ without evidence of disease
  • adequately treated breast ductal carcinoma in situ without evidence of disease
  • prostatic intraepithelial neoplasia without evidence of prostate cancer

Other

• Inability to swallow or absorb tablets
• Subject considered unsuitable for study for any other reason in the physician's best judgement. Before excluding a potential subject, please consult the sponsor.

• Ph positive \[either t(9;22) and/or BCR-ABL1 positive\] ALL, CD19 positive
• Age ≥18 years at time of informed consent
• No prior induction treatment for ALL. A brief corticosteroid pre-phase (\< 1 week), or hydroxyurea for cytoreduction or symptom control is permitted.
  • 3\. Greater than or equal to 5% blasts in the BM.
  • 4\. Performance status ≤2 (ECOG Scale, see Appendix IV)
  • 5\. Adequate organ function: 5.1.5.1 Hepatic:
  • Adequate liver function as defined by the following criteria (unless the increased values are judged to be leukemia disease related):
  • Total serum bilirubin less than 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome or Meulengracht disease Alanine aminotransferase (ALT) less than 3 x ULN Aspartate aminotransferase (AST) less than 3 x ULN 5.1.5.2 Pancreatic:
• Serum lipase less than 2 x ULN 5.1.5.3 Renal:
• Estimated Creatinine clearance ≥ 40 mL/min 5.1.5.4 Cardiac:
• Left ventricular ejection fraction \> 40%