CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation

NCT ID: NCT02893189

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-27
• Study Completion Date: 2022-12-31

Brief Summary

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.

Detailed Description

Patients will receive escalating doses of 4G7-CARD T-cells (after pre-conditioning with Fludarabine and Cyclophosphamide), paralleling clinical standard of care with unmanipulated donor lymphocytes. Intra-patient dose escalation will proceed at intervals of not less than 8 weeks, dependent on development of toxicity or evidence of efficacy and confirmation by the Trial Management Group.

Three dose cohorts levels are planned, and dosing will be according to total CD3+ T- cell dose as this correlates with toxicity in the unmanipualated donor lymphocyte setting:

• Dose Level 1: 1x10^6 CD3+ T-cells/kg (starting dose for all patients)
• Dose Level 2: 3x10^6 CD3+ T-cells/kg
• Dose Level 3: 1x10^7 CD3+ T-cells/kg

The inter-patient dosing for the first 3 patients was at least 28 days, following TMG confirmation.

Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. During the long term follow up phase of the study (years 2-3 post-final 4G7-CARD T-cell infusion) patients will be followed-up annually for overall survival, disease status and safety.

All patients will enter long term follow up until 3 years post-final 4G7-CARD T-cell infusion.

Conditions

CD19+ Malignancies: Relapse Post-allogeneic Transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

4G7-CARD T-cells

All patient will receive modified CAR19 T-cells.

Group Type: EXPERIMENTAL

Infusion of modified CAR19 T-cells (4G7-CARD T-cells)

Intervention Type: GENETIC

The original stem cells donor (or if not available the patient) will undergo unstimulated leucapheresis for generation of the Advanced Therapy Interventional Medicinal Product (ATIMP) 4G7-CARD T-cells. Escalating doses of the ATIMP will then be infused to the patient depending on outcome and any experienced side effects.

Interventions

Infusion of modified CAR19 T-cells (4G7-CARD T-cells)

The original stem cells donor (or if not available the patient) will undergo unstimulated leucapheresis for generation of the Advanced Therapy Interventional Medicinal Product (ATIMP) 4G7-CARD T-cells. Escalating doses of the ATIMP will then be infused to the patient depending on outcome and any experienced side effects.

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl Peggs

Role: PRINCIPAL_INVESTIGATOR

University College London Hospital

Locations

University College London Hospital

London, , United Kingdom

Countries

United Kingdom

References

Roddie C, Dias J, O'Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, Bosshard-Carter L, Mitsikakou M, Charalambous E, Mehra V, Roddy H, Cheung GW, Hartley JA, Mahmoud N, Ensell L, Patel Y, Marzolini MAV, Farzaneh F, Nickolay L, Himoudi N, Syed F, Popova B, Galani S, Day A, Lowdell MW, Peggs KS. Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion. Blood. 2025 Oct 2;146(14):1664-1676. doi: 10.1182/blood.2025028790.

Reference Type: DERIVED

PMID: 40643148 (View on PubMed)

O'Reilly M, Roddie C, Marzolini MAV, Rodriguez-Justo M, Pomplun S, Pule M, Peggs KS. Trafficking of CAR T cells to sites of subclinical leukaemia cutis. Lancet Oncol. 2020 Mar;21(3):e179. doi: 10.1016/S1470-2045(19)30861-7. No abstract available.

Reference Type: DERIVED

PMID: 32135121 (View on PubMed)

Other Identifiers

UCL16/0045

Identifier Type: -

Identifier Source: org_study_id