Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study) - PRISM

Exclusion Criteria

• Exclusion Criteria For All Arms:
• 1. History of prior malignancy except for the following: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years
• before screening and felt to be at low risk for recurrence by treating physician, b) Adequately treated lentigo maligna melanoma without current evidence of disease
• or adequately controlled nonmelanomatous skin cancer, c) Adequately treated carcinoma in situ without current evidence of disease, d) Evidence of severe or
• uncontrolled systemic disease, or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, history of, or active, bleeding
• diatheses or uncontrolled active systemic fungal, bacterial, viral, or other infection, or intravenous anti-infective treatment within 2 weeks before first dose of study
• treatment.
• 2. Serologic status reflecting active hepatitis B or C infection.
• 3. Prior use of standard antilymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment (not including palliative radiotherapy or
• palliative corticosteroid use).
• 4. Requires ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid cancer or other conditions.
• 5. For subjects under DLT review only: Any haematopoietic growth factors or darbepoetin within 14 days of the first dose of study treatment.
• Exclusion Criteria for Arm 1:
• 1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
• 2. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive
• small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and
• bariatric surgery, such as gastric bypass.
• 3. Requires treatment with proton-pump inhibitors.
• 4. Requires treatment with strong CYP3A inhibitors or inducers.
• Exclusion Criteria for Arm 2:
• 1. Relative hypotension (< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of >20 mm Hg.
• 2. Uncontrolled hypertension requiring clinical intervention.
• 3. At risk for brain perfusion problems based on medical history.
• 4. Mean resting QT interval (QTc) calculated using Fridericia’s formula (QTcF) >470 msec for female subjects and >450 msec for male subjects obtained from 3
• electrocardiograms (ECGs), or congenital long QT syndrome.
• 5. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
• 6. Known to have tested positive for human immunodeficiency virus (HIV) & requires treatment with restricted medications.
• 7. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive
• small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and
• bariatric surgery, such as gastric bypass.
• 8. Requires treatment with proton-pump inhibitors.
• Exclusion Criteria for Arm 3:
• 1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
• 2. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive
• small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and
• bariatric surgery, such as gastric bypass.
• 3. Requires treatment with proton-pump inhibitors.
• 4. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening.
• 5. History of haemolytic anaemia or Evans syndrome in the last 3 months before enrolment.
• 6. Positive IgG component of the direct antiglobulin test (DAT).
• 7. Prior treatment with CD47 or SIRPα-targeting agents.
• 8. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab
• Exclusion Criteria for Arm 4:
• 1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
• 2. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive
• small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and
• bariatric surgery, such as gastric bypass.
• 3. Requires treatment with proton-pump inhibitors.
• 4. Requires treatment with CYP3A inhibitors or inducers or substrates of drug transporters.
• 5. History of tuberculosis.
• 6. Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); clinically important ECG findings, or risk factors for QTc prolongation.
• 7.Subjects receiving antiplatelet or anticoagulant therapies within 28 days of first dose of study drug.