TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL)

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    10
  • sponsor
    Great Ormond Street Hospital for Children NHS Foundation Trust
Updated on 27 January 2021

Summary

PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCR-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. They have been transduced to express and anti-CD19 chimeric antigen receptor (CAR19) using a lentiviral vector that also incorporates CRISPR guides for genome editing of CD52 and TRAC loci in the presence of transiently provided Cas9.

Recognition by TT52CAR19 T cells mediates eradication of CD19+ leukaemia and other CD19+ B cells through T cell mediated cytotoxicity.

This study aims to apply PBLTT52CAR19 T cells to secure molecular remission in children with relapsed/refractory B-ALL ahead of programmed allogeneic stem cell transplantation. The cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.

Details
Condition B Acute Lymphoblastic Leukemia, B-cell Acute Lymphoblastic Leukemia, pro b
Treatment PBLTT52CAR19
Clinical Study IdentifierNCT04557436
SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-SCT) or refractory (not achieving an initial complete response (CR) after 2 cycles of standard chemotherapy) CD19-positive B-acute lymphoblastic leukaemia
Morphologically confirmed with leukemic blasts in the bone marrow or a quantifiable MRD load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
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 50 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
CD19-negative B-cell leukaemia
Evidence of disease progression after cytoreduction
Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer National guidelines). Patients developing grade 3 CNS disease at any time after enrolment will be excluded
Absence of suitable HLA matched or mismatched donor
Weight < 6 kgs
Presence of donor-specific anti-HLA antibodies directed against PBLTT52CAR19
GvHD requiring systemic therapy
Systemic steroid therapy prednisolone >0.5mg/kg/day
Known hypersensitivity to any of the test materials or related compounds
Active bacterial, fungal, or viral infection not controlled by a 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 anti-fungal 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
Intrathecal methotrexate within 4 weeks or intrathecal chemotherapy (e.g Ara-C) within 2 weeks of lymphodepletion
Less than 2 half-lives from prior therapy with immune checkpoint pathway modifiers to lymphodepletion
Prior CAR19 therapy known to be associated with Grade 3 cytokine release syndrome (CRS) or Grade 3 drug-related CNS toxicity
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