Safety of Immune Cells for Patients with Relapsed Leukaemia or Lymphoma after Chemotherapy
A Phase I Study of Autologous CD19 Specific Chimeric Antigen Receptor T-cells for Therapy of Relapsed and Refractory B-cell Leukaemia and Lymphoma
Western Sydney Local Health District, Westmead Hospital
20 participants
Mar 1, 2019
Interventional
Conditions
Summary
The aim of this project is to evaluate the Safety of Immune Cells for Patients with Relapsed Leukaemia or Lymphoma after chemotherapy. Who is it for? You may be eligible to join this study if you have persistent or relapsed B-cell malignancy after standard chemotherapy. Study details Patient 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 Criteria12
- Any patient regardless of sex or age with relapsed or refractory disease after standard therapy. Disease may be identified by clinical examination, radiology, nuclear imaging, flow cytometry or molecular biological methods. To qualify for enrolment, patients must have one of the following:
- Refractory CD19+ high grade NHL- defined as less than 50% reduction in lymph node size (nodes >2cm) or persisting organ enlargement or the appearance of new lymphadenopathy, hepatosplenomegaly or marrow involvement after chemotherapy or Deauville 5 PET positive disease on interim PET scan after 4 cycles of chemotherapy
- Relapsed CD19+ high grade NHL ineligible for autologous stem cell transplant or after autologous stem cell transplant
- Refractory CD19+ low grade NHL- defined as less than 50% reduction in lymph node size (nodes >2cm) or persisting organ enlargement or the appearance of new lymphadenopathy, hepatosplenomegaly or marrow involvement after chemotherapy
- Relapsed CD19+ low grade NHL less than 12 months from chemotherapy or third or greater relapse
- Refractory CLL defined as resistance to purine analogues with less than 50% reduction in lymph node size (nodes >2cm) and/or lymphocytosis, or persisting organ enlargement after initial therapy or progression/relapse requiring therapy less than 6 months post chemotherapy.
- CLL Richters transformation
- Persistent CD19+ ALL after consolidation, defined as not in CR by morphology, flow, cytogenetics or molecular methods after induction chemotherapy (includes MRD at or above threshold as assessed by flow cytometry or molecular methods)
- Relapsed CD19+ ALL as assessed by morphology, flow, cytogenetics or molecular methods at any time point during or after standard therapy
- Karnofsky/Lansky score greater than or equal to 50%, or ECOG less than or equal to 2.
- 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.
- Patient and/or parent/guardian capable of providing informed consent.
Exclusion Criteria6
- Uncontrolled inter-current infection.
- Bilirubin >2x upper limit of normal, AST >3x upper limit of normal, creatinine >2x upper limit of normal for age.
- Pulse oximetry greater 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 autologous CD19-specific chimeric antigen receptor (CAR19) T-cells for relapsed or persistent B-cell malignancy after standard chemotherapy. Patients will have T-cells collected from their blood by leukapheresis. This involves having drips placed into the large veins in the patient's arms which are then connected to an apheresis machine for several hours. These T-cells will undergo genetic modification in the laboratory to express the CAR19 and be frozen for administration to the patient once they are ready to receive them. 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. Autologous CAR19 T-cells will be administered intravenously after lymphodepleting cyclophosphamide 250mg/m^2 and fludarabine 40mg/m^2 tablets taken orally, daily on days -4 to -2 prior to CAR19 T-cell administration by intravenous injection 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(11)
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ACTRN12619000079145