Ignite Creation Date:
2025-12-24 @ 6:56 PM
Ignite Modification Date:
2026-01-20 @ 11:31 PM
Study NCT ID:
NCT02935257
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-23
First Post:
2016-10-14
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19
Sponsor:
University College, London
Organization:
Study Overview
Official Title:
Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ALLCAR19
Brief Summary:
This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with (1) high risk, relapsed/refractory (r/r) CD19+ B-ALL; (2) r/r DLBCL; (3) r/r CLL/SLL and (4) r/r FL and (5) r/r MCL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with the lentiviral pCCL.PGK.alpha.CD19CAT-41BBzeta vector, CD19CAT-41BBζ CAR T-cells (referred to subsequently as CD19CAR T-cells) which is classified as a gene therapy medicinal product. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP. The ATIMP will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL, DLBCL, B-CLL/SLL, FL and MCL.
Recruitment into the ALL cohort has been completed and no further patients with ALL are being treated on the study.
Patients receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only will also receive a single dose of pembrolizumab 200 mg at day -1.
Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.
* Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10\^6 CD19 CAR T-cells and a possible second dose of 310 x 106 CAR T-cells
* Regimen A2: Patients with B-ALL with a baseline marrow blast% of \>20% receive a split dose with a first dose of 10 x 10\^6 CD19CAR T-cells and a possible second dose of 400 x 10\^6 CAR T-cells
* Regimen B: Patients with DLBCL receive a single dose of 200 x 10\^6 CAR T-cells
* Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 106 CD19 CAR T-cells and a possible second dose of 200 x 10\^6 CD19 CAR T-cells.
* Regimen D: Patients with FL and MCL receive a single dose of 200 x 10\^6 CAR T-cells
The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.
After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, enter long term follow up until 10 years post-CD19CAR T-cell infusion.
Recruitment into the ALL cohort has been completed and no further patients with ALL are being treated on the study.
Patients receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only will also receive a single dose of pembrolizumab 200 mg at day -1.
Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.
* Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10\^6 CD19 CAR T-cells and a possible second dose of 310 x 106 CAR T-cells
* Regimen A2: Patients with B-ALL with a baseline marrow blast% of \>20% receive a split dose with a first dose of 10 x 10\^6 CD19CAR T-cells and a possible second dose of 400 x 10\^6 CAR T-cells
* Regimen B: Patients with DLBCL receive a single dose of 200 x 10\^6 CAR T-cells
* Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 106 CD19 CAR T-cells and a possible second dose of 200 x 10\^6 CD19 CAR T-cells.
* Regimen D: Patients with FL and MCL receive a single dose of 200 x 10\^6 CAR T-cells
The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.
After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, enter long term follow up until 10 years post-CD19CAR T-cell infusion.
Detailed Description:
This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with (1) high risk, relapsed/refractory (r/r) CD19+ B-ALL; (2) r/r DLBCL; (3) r/r CLL/SLL, (4) r/r FL and (5) r/r MCL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with the lentiviral pCCL.PGK.alpha.CD19CAT-41BBζ vector, CD19CAT-41BBζ CAR T-cells (referred to sub-sequently as CD19CAR T-cells) which is classified as a gene therapy medicinal product. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP. The ATIMP take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. The study evaluates ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL, DLBCL, B-CLL/SLL, FL and MCL.
The ALL and FL cohorts are now completed and no further patients with ALL or FL are treated on the study.
Patients receive lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only also receive a single dose of pembrolizumab 200 mg at day -1.
Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.
* Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10\^6 CD19 CAR T-cells and a possible second dose of 310 x 10\^6 CAR T-cells
* Regimen A2: Patients with B-ALL with a baseline marrow blast% of \>20% receive a split dose with a first dose of 10 x 10\^6 CD19CAR T-cells and a possible second dose of 400 x 106 CAR T-cells
* Regimen B: Patients with DLBCL receive a single dose of 200 x 10\^6 CAR T-cells
* Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 10\^6 CD19 CAR T-cells and a possible second dose of 200 x 106 CD19 CAR T-cells.
* Regimen D: Patients with indolent B-NHL receive a single dose of 200 x 10\^6 CAR T-cells
The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.
After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 10 years post-CD19CAR T-cell infusion.
The ALL and FL cohorts are now completed and no further patients with ALL or FL are treated on the study.
Patients receive lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only also receive a single dose of pembrolizumab 200 mg at day -1.
Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.
* Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10\^6 CD19 CAR T-cells and a possible second dose of 310 x 10\^6 CAR T-cells
* Regimen A2: Patients with B-ALL with a baseline marrow blast% of \>20% receive a split dose with a first dose of 10 x 10\^6 CD19CAR T-cells and a possible second dose of 400 x 106 CAR T-cells
* Regimen B: Patients with DLBCL receive a single dose of 200 x 10\^6 CAR T-cells
* Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 10\^6 CD19 CAR T-cells and a possible second dose of 200 x 106 CD19 CAR T-cells.
* Regimen D: Patients with indolent B-NHL receive a single dose of 200 x 10\^6 CAR T-cells
The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.
After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 10 years post-CD19CAR T-cell infusion.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: