Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation
COBALT
COBALT: Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation
2 other identifiers
interventional
10
1 country
1
Brief Summary
The purpose of this study is to administer novel cluster of differentiation antigen 19 (CD19) specific Chimeric Antigen Receptor T-cells (CAR19 T-cells) to patients with relapsed or resistant Diffuse Large B Cell Lymphoma (DLBCL) to assess the safety and efficacy of this strategy as a bridge to allogeneic transplantation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 23, 2015
CompletedFirst Posted
Study publicly available on registry
May 1, 2015
CompletedStudy Start
First participant enrolled
June 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 21, 2022
CompletedApril 28, 2023
April 1, 2023
3.7 years
March 23, 2015
April 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Feasibility of adequate leucapheresis collection and generation of CAR19 T cells.
The number of CAR19 T cells successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
1 month
Toxicity evaluation following CAR19 T-cell administration.
Toxicity will be examined for each patient receiving CAR19 T cells, using the maximum grade for each toxicity type, all summarized as number of patients with adverse events.
1 year
Efficacy of CAR19 T-cells.
Efficacy will be defined as the number of patients that meet the clinical complete responders criteria.
1 year
Secondary Outcomes (5)
CAR19 T-cell engraftment
1 year
B cell compartment
1 year
Cytokine profile
1 year
Clinical complete response
1 month
Eligibility to allogeneic transplantation
1-3 years
Study Arms (1)
CAR19 T-cells
EXPERIMENTALPatients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine. The CAR19 T-cells are to be administered on day 0.
Interventions
Patients will undergo leukapheresis prior to pre-conditioning chemotherapy to provide the immune cells required to produce the therapeutic product.
Patients will receive a standard pre-conditioning regime with cyclophosphamide 60mg/kg/day IV over 1 hour for 2 days (day-7 and day-6).
Fludarabine 25mg/m2/day IV over 15/30 minutes for 5 days (Day-5 to day-1).
The CAR19 T-cells are to be administered on day 0 at the dose specified by the Cancer Trials Centre (CTC) at the time of registration. Three dose cohorts are planned: * Dose Level 1: 2x105 CAR19 T-cells/kg * Dose Level 2: 1x106 CAR19 T-cells/kg * Dose Level 3: 5x106 CAR19 T-cells/kg
Eligibility Criteria
You may qualify if:
- Age 16-65 years
- Confirmed diagnosis of CD19+ DLBCL
- Primary resistant or relapsed disease failing to achieve metabolic Complete Response (CR) to 1st line salvage, or relapse post autograft failing to achieve metabolic CR following a single further cycle of salvage
- Potential allogeneic transplant candidate
- Agreement to have a pregnancy test, use adequate contraception for 12 months post-CAR19 T-cell infusion
- Karnofsky performance status \>60
- Written informed consent
You may not qualify if:
- Women who are pregnant or lactating
- Prior allogeneic transplantation
- Progressive disease following most recent salvage prior to planned leucapheresis (those with mixed response are eligible)
- Prior history of ischaemic heart disease, dysrhythmias, abnormal electrocardiogram (ECG)(Left Bundle Branch Block (LBBB)), Multiple Gated Acquisition (MUGA) left ventricular ejection fraction (LVEF) \<40%
- Known central nervous system (CNS) involvement or cerebral vascular accident (CVA) within prior 3 months
- Patients receiving corticosteroids at a dose of \> 10mg prednisolone per day (or equivalent)
- Use of rituximab within the last 2 months prior to CAR19 T-cell infusion
- Active autoimmune disease requiring immunosuppression
- Life expectancy \<3 months
- Known allergy to albumin or dimethylsulfoxide (DMSO)
- Any contraindication to the administration and use of ifosfamide, epirubicin, etoposide, fludarabine and cyclophosphamide.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University College London Hospital
London, United Kingdom
Related Publications (1)
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Karl Peggs
University College, London
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 23, 2015
First Posted
May 1, 2015
Study Start
June 1, 2016
Primary Completion
February 2, 2020
Study Completion
March 21, 2022
Last Updated
April 28, 2023
Record last verified: 2023-04