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Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7) (TvT CAR7)

Primary Purpose

Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)
Sponsored by
Great Ormond Street Hospital for Children NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

Eligibility Criteria

6 Months - 16 Years (Child)All SexesDoes not accept healthy volunteers

Demographic characteristics:

  1. Male or female patients
  2. Age ranging between 6 months and <16 years

Medical and therapeutic criteria:

  1. Relapsed/refractory T cell malignancy ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable MRD load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
  2. CD7+ (>99%) leukaemia associated immunophenotype (LAIP)
  3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
  4. Estimated life expectancy ≥12 weeks
  5. Lansky (age <16 years at the time of assent/consent) or Karnofsky (age ≥16 years at the time of assent/consent) performance status ≥70; Eastern Cooperative Oncology Group ECOG performance status < 2

Exclusion Criteria:

  1. Patients/parents unwilling to undergo a follow-up for 15 years
  2. Foreseeable poor compliance to the study procedures
  3. Evidence of disease progression after cytoreduction
  4. Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines)
  5. Absence of suitable HLA matched or mismatched donor
  6. Weight <6 kg
  7. Presence of donor-specific anti-HLA antibodies directed against BE-CAR7
  8. GvHD requiring systemic therapy
  9. Systemic steroid therapy prednisolone >0.5 mg/kg/day
  10. Known hypersensitivity to any of the test materials or related compounds
  11. Active bacterial, fungal or viral infection not controlled by standard of care anti-microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or antifungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy.
  12. Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion.
  13. Lactating female participants unwilling to stop breastfeeding
  14. Prior CAR therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity

Sites / Locations

  • Ilyas AliRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7

Arm Description

Single-dose intravenous infusion (weight-based dosing) of CAR7+ T cells/kg BECAR7 Total duration of treatment: 28 days Follow-up: 12 months Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-7 infusion. Patients will then receive a single infusion of the BE CAR-7 cells and will be closely monitored in hospital via blood and bone marrow tests for safety and to check the levels of BE CAR-7 and leukaemia cells. Patients are expected to be in hospital for 4-6 weeks for the BE CAR-7 therapy and the transplant will be scheduled 2-4 weeks after the end of BE CAR7 if leukaemia cells are no longer detectable. Patients will be monitored on the study for 1 year every month for the first 3 months and then every 6 months and then long term in routine clinics.

Outcomes

Primary Outcome Measures

Frequency and description of adverse events after BE-CAR7 infusion
Incidence of Grade 3-5 toxicities occurring from infusion up to one year follow-up. Severe Adverse Reactions of special interest will be CRS, ICANS and GvHD. American Society of Bone Marrow Transplantation grading scales for CRS/ICANS and National Institute of Health criteria for GVHD will be applied. Commo Terminology Criteria nomenclature will be used to grade other adverse events.

Secondary Outcome Measures

Number of patients achieving disease remission ahead of allo-SCT
Remission rate will be assessed by bone marrow and CNS evaluation after 28 days. Disease remission is defined as morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with MRD <10e-3 by flow and/or PCR.

Full Information

First Posted
May 13, 2022
Last Updated
June 30, 2023
Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborators
UCL Great Ormond Street Institute of Child Health, Medical Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT05397184
Brief Title
Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)
Acronym
TvT CAR7
Official Title
Phase 1 Study of Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 19, 2022 (Actual)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborators
UCL Great Ormond Street Institute of Child Health, Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
T-cell leukaemia is an uncommon type of blood cell cancer that affects white blood cells (T cells). This phase I clinical trial will treat children aged 6 months up to 16 years with T cell leukaemia which has come back (relapsed) after chemotherapy or is not responding to chemotherapy (refractory). The cell therapy is made from white blood cells (T cells) collected from a healthy donor and changed so they can kill other T cells, including leukaemia cells. These 'ready-made' CAR T cells have been made using a new technique called CRISPR base editing to modify them DNA code and have been given the name BE CAR-7. This technique allows them to work after chemotherapy and also disarms them to prevent effects against normal cells. The main aim of this study is to assess the safety of the BE CAR-7 treatment and to see if ready-made CAR T cells can eradicate T cell leukaemia ahead of a planned bone marrow transplant.
Detailed Description
Who can participate? Patients aged 6 months to 16 years with relapsed/refractory T cell leukaemia ahead of a planned bone marrow transplant What does the study involve? Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-7 infusion to improve the ability of T-cells to establish and grow. Patients will then receive a single infusion of the BE CAR-7 cells and will be closely monitored in hospital. Patients are expected to be in hospital for 4-6 weeks for the BE CAR-7 treatment and the transplant will be scheduled 2-4 weeks after the end of BE CAR7 if leukaemia cells are no longer detectable. Patients will be monitored on the study for 1 year after transplant and then long term in routine clinics. What are the possible benefits and risks of participating? Taking part in the study of testing 'ready-made' CAR T cells could help reduce the amount of disease and get the patient into remission before a bone marrow transplant. Leukaemia is less likely to come back after a bone marrow transplant if levels in the bone marrow are undetectable. The ready-made CAR T cells are being used to try and improve the chances of successful transplantation. Side effects may include low blood cell counts, infections, cytokine storm (severe immune reaction), graft versus host disease (where the donated cells attack the body) and other complications.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase 1, open label, non randomised
Masking
None (Open Label)
Masking Description
Not applicable (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7
Arm Type
Experimental
Arm Description
Single-dose intravenous infusion (weight-based dosing) of CAR7+ T cells/kg BECAR7 Total duration of treatment: 28 days Follow-up: 12 months Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-7 infusion. Patients will then receive a single infusion of the BE CAR-7 cells and will be closely monitored in hospital via blood and bone marrow tests for safety and to check the levels of BE CAR-7 and leukaemia cells. Patients are expected to be in hospital for 4-6 weeks for the BE CAR-7 therapy and the transplant will be scheduled 2-4 weeks after the end of BE CAR7 if leukaemia cells are no longer detectable. Patients will be monitored on the study for 1 year every month for the first 3 months and then every 6 months and then long term in routine clinics.
Intervention Type
Biological
Intervention Name(s)
Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)
Other Intervention Name(s)
BECAR7
Intervention Description
Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR7+ T cells/kg BECAR7 Total duration of treatment: 28 days Follow-up: 12 months
Primary Outcome Measure Information:
Title
Frequency and description of adverse events after BE-CAR7 infusion
Description
Incidence of Grade 3-5 toxicities occurring from infusion up to one year follow-up. Severe Adverse Reactions of special interest will be CRS, ICANS and GvHD. American Society of Bone Marrow Transplantation grading scales for CRS/ICANS and National Institute of Health criteria for GVHD will be applied. Commo Terminology Criteria nomenclature will be used to grade other adverse events.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of patients achieving disease remission ahead of allo-SCT
Description
Remission rate will be assessed by bone marrow and CNS evaluation after 28 days. Disease remission is defined as morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with MRD <10e-3 by flow and/or PCR.
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Demographic characteristics: Male or female patients Age ranging between 6 months and <16 years Medical and therapeutic criteria: Relapsed/refractory T cell malignancy ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable MRD load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) CD7+ (>99%) leukaemia associated immunophenotype (LAIP) Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available Estimated life expectancy ≥12 weeks Lansky (age <16 years at the time of assent/consent) or Karnofsky (age ≥16 years at the time of assent/consent) performance status ≥70; Eastern Cooperative Oncology Group ECOG performance status < 2 Exclusion Criteria: Patients/parents unwilling to undergo a follow-up for 15 years Foreseeable poor compliance to the study procedures Evidence of disease progression after cytoreduction Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines) Absence of suitable HLA matched or mismatched donor Weight <6 kg Presence of donor-specific anti-HLA antibodies directed against BE-CAR7 GvHD requiring systemic therapy Systemic steroid therapy prednisolone >0.5 mg/kg/day Known hypersensitivity to any of the test materials or related compounds Active bacterial, fungal or viral infection not controlled by standard of care anti-microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or antifungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy. Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion. Lactating female participants unwilling to stop breastfeeding Prior CAR therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Chiesa, Dr
Phone
020 7405 9200
Ext
8434
Email
Robert.Chiesa@gosh.nhs.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Agnieszka B Kubat, MSc
Phone
07502269573
Email
a.kubat@ucl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Waseem Qasim, Professor
Organizational Affiliation
Great Ormond Street Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ilyas Ali
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ilyas Ali, MSc
Phone
+44 (0)207 905 2863
Email
Ilyas.Ali@gosh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Vanshree Patel, Dr
Phone
+44 (0)207 905 2863
Email
Vanshree.Patel@gosh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Waseem Qasim, Professor
First Name & Middle Initial & Last Name & Degree
Robert Chiesa, Dr
First Name & Middle Initial & Last Name & Degree
Ajay Vora, Professor

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)

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