Safety of Immune Cells for Patients with Relapsed Leukaemia or Lymphoma after Bone Marrow Transplant
A Phase I Study of CD19 Specific Chimeric Antigen Receptor T-cells for Therapy of Persistent and Relapsed B-cell Leukaemia and Lymphoma Post Allogeneic Stem Cell Transplantation
Western Sydney Local Health District, Westmead Hospital
20 participants
Dec 4, 2017
Interventional
Conditions
Summary
The aim of this project is to evaluate the Safety of Immune Cells for Patients with Relapsed Leukaemia or Lymphoma after Bone Marrow Transplant. Who is it for? You may be eligible to join this study if you have persistent or relapsed B-cell malignancy post related donor allogeneic stem cell transplant and a donor willing and available to donate peripheral blood for the generation of CAR19 T-cells. Study details Matched related donor derived CAR19 T-cells will be administered intravenously after lymphodepleting cyclophosphamide and fludarabine. This T-cell therapy may be administered alone or in addition to salvage chemotherapy. Three CAR19 T-cell dose levels will be assessed within each patient: 1x10^7cells/m^2, 5x10^7cells/m^2 and 1x10^8/m^2. Dose escalation will be determined 4 weeks after the last dose dependent on persistence of disease, no severe toxicity and falling CAR19 T-cell numbers. Patients will be monitored for early and long term toxicity, persistence of CAR T-cells and disease response. If successful, this treatment will enable the widespread application of CAR19 T-cells to patients with few other effective treatment options.
Eligibility
Inclusion Criteria6
- Any patient regardless of sex or age with persistent or recurrent disease after a matched related allogeneic stem cell transplant performed for CD19+ lymphoid malignancies. Disease may be identified by clinical examination, radiology, nuclear imaging, flow cytometry or molecular biological methods.
- Life expectancy greater than or equal to 6 weeks.
- Karnofsky/Lansky score greater than or equal to 50%, or ECOG less than or equal to 2.
- Donor willing and available to donate peripheral blood for the generation of CAR19 T-cells.
- Sexually active patients must be willing to utilise one of the more effective birth control methods for 6 months after the CTL infusion. Male partners should use a condom.
- Donor and patient and/or parent/guardian capable of providing informed consent.
Exclusion Criteria9
- Uncontrolled inter-current infection.
- Graft versus host disease greater than or equal to grade II.
- Unmanipulated donor lymphocyte infusion within the previous 10 weeks.
- Corticosteroid dose greater than the equivalent of 0.5mg/kg of oral prednisolone.
- Bilirubin >2x upper limit of normal, AST >3x upper limit of normal, creatinine >2x upper limit of normal for age.
- Pulse oximetry less than or equal to 90% on room air.
- Pregnant or lactating.
- History of hypersensitivity reactions to murine protein-containing products.
- History of seizures.
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Interventions
Up to 20 patients will receive allogeneic matched sibling donor derived CD19-specific chimeric antigen receptor (CAR19) T-cells for relapsed or persistent B-cell malignancy detected at any time post allogeneic stem cell transplant. Patients with active disease requiring therapy while CAR19 T-cells are being prepared will receive chemotherapy or radiotherapy as appropriate determined by the patient's usual treating physician. Matched related donor derived CAR19 T-cells will be administered intravenously after lymphodepleting cyclophosphamide 250mg/m^2 IV and fludarabine 25mg/m^2 IV daily on days -4 to -2 prior to CAR19 T-cell administration on day 0. Three CAR19 T-cell dose levels will be assessed within each patient: 1x10^7cells/m^2, 5x10^7cells/m^2 and 1x10^8/m^2. Patients will receive 1 dose only at each level. Dose escalation will be determined 4 weeks after the last dose dependent on persistence of disease, no severe toxicity and falling CAR19 T-cell numbers.
Locations(3)
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ACTRN12617001579381