VICTORY: This phase I study is assessing the safety and appropriate dose level of targeted therapy (venetoclax) before treatment with chemotherapy drugs (fludarabine and cyclophosphamide) in people with certain blood cancers or disorders who are planned to undergo allogenic haematopoietic stem cell transplantationA Phase I Study of Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation

Exclusion

Patients will be excluded from this study if any of the following criteria are met:

• Moderate or high risk of tumour lysis syndrome prior to conditioning for allogeneic transplantation, defined as:

  1. For CLL: Diameter of any lymph node or tumour mass >5cm OR absolute lymphocyte count≥25x10^9/L
  2. For NHL: Diameter of any lymph node or tumour mass >5cm

• Prior intolerance of venetoclax or another BCL-2 inhibitor with the exception of cytopenias. Patients with prior clinical tumour lysis syndrome following venetoclax or other BCL-2 inhibitor will be excluded from the study if at the time of prior TLS their disease burden was as follows:

  1. For CLL: Diameter of any lymph node or tumour mass <5cm OR absolute lymphocyte count≤25x10^9/L
  2. For NHL: Diameter of any lymph node or tumour mass <5cm
• Reticulin fibrosis of the marrow of grade MF 2-3
• Prior allogeneic stem cell transplantation
• Haemopoietic cell transplantation - comorbidity index (HCT-CI) score > 5
• Any currently active malignancy other than the primary indication for alloSCT (except localized basal cell carcinoma or squamous cell carcinoma of the skin)
• Uncontrolled systemic infection
• Known malabsorption syndrome
• Has received within 7 days prior to the first dose of venetoclax CYP3A4 inducers such as rifampicin, carbamazepine, phenytoin and St John's wort
• Has received within 7 days prior to the first dose of venetoclax CYP3A4 inhibitors
• Known positivity to HIV
• Significant physical or psychiatric comorbid illness that in the investigator's opinion would impair the patient's ability to participate in the study.