CD19+ Malignancies: Relapse Post-allogeneic Transplant Clinical Trial
— CARDOfficial title:
Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)
| Verified date | June 2023 |
| Source | University College, London |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned. Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.
| Status | Completed |
| Enrollment | 17 |
| Est. completion date | December 31, 2022 |
| Est. primary completion date | December 31, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 16 Years to 70 Years |
| Eligibility | Inclusion Criteria: 1. Age 16-70 years 2. Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation 3. Agreement to have a pregnancy test, use adequate contraception for 12 months post-final 4G7-CARD T-cell infusion 4. Karnofsky performance status >60 5. Written informed consent Exclusion Criteria: 1. Women who are pregnant or lactating 2. Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if performed) 3. Known involvement of the central nervous system or cerebral vascular accident within prior 3 months 4. Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent) 5. Active graft versus host disease requiring immunosuppression 6. Use of rituximab within the last 2 months prior to ATIMP infusion 7. Known allergy to albumin or dimethyl sulfoxide (DMSO) 8. Patients who have experienced significant neurotoxicity following blinatumomab treatment |
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | University College London Hospital | London |
| Lead Sponsor | Collaborator |
|---|---|
| University College, London |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system | The number of ATIMP successfully manufactured would be assessed for all registered patients | Through patient registration and manufacturing period, an average of 18 months from start of trial | |
| Primary | Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions. | Toxicity evaluation following 4G7-CARD T-cell administration as evaluated by the occurrence of adverse events per studied dose using CTCAE v4.03, defined as >grade 2 events that are causally related to study treatment or procedure or Serious Adverse Reactions that require withdrawal of the patient from the study; development and severity of graft-versus-host-disease (GvHD) following cell infusion will also be evaluated as a potential toxicity, as well as development and severity of cytokine release syndrome / macrophage activation syndromes assessed by 'University of Pennsylvania' criteria | Up to 3 years post final 4G7-CARD T-cell infusion | |
| Secondary | Assessment of engraftment, expansion and persistence of the 4G7-CARD T-cells as determined by quantitative polymerase chain reaction (qPCR) or flow cytometry | Data for engraftment and expansion would be summarised by mean, median or interquartile ranges and a Kaplan Meier plot for persistence | Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion | |
| Secondary | Assessing the depletion of B cell compartment, as determined by flow cytometry | Data would be summarised using means (medians) and as the percentage reduction from baseline | Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion | |
| Secondary | Assessing the timing and magnitude of cytokine release, evaluated using Cytokine bead arrays | Data on timing (kinetic of change) and magnitude of cytokine levels can be summarised using means (medians) and plots for each patients | Sampling occurs at days 0, 4, 6, 11, 18, plus 1 month post final 4G7-CARD T-cell infusion |