Status:
TERMINATED
CD19-CAR Immunotherapy for Childhood Acute Lymphoblastic Leukemia (ALL)
Lead Sponsor:
University College, London
Collaborating Sponsors:
European Union
The Leukemia and Lymphoma Society
Conditions:
Acute Lymphoblastic Leukemia
Eligibility:
All Genders
Up to 18 years
Phase:
PHASE1
PHASE2
Brief Summary
The aim of this clinical trial is to evaluate the feasibility, safety and biological effect of adoptive transfer of CD19ζ chimaeric receptor transduced donor-derived EBV-specific cytotoxic T-lymphocyt...
Eligibility Criteria
Inclusion
- Inclusion Criteria Pre-emptive arm
- Children (18 years or younger) with CD19+ precursor B cell ALL fulfilling one of the following criteria who are undergoing an allogeneic stem cell transplant from an EBV-seropositive donor:
- In first remission, if at least one of the following criteria are met:
- t(9;22) and MRD positive (BCR-ABL/ABL ratio \> 0.01%) after HR3 block of EsPhALL or pre-HSCT or
- Infant ALL age \< 6 months at diagnosis with MLL gene rearrangement and either presenting wcc \>300 x 10\^9/L or poor steroid early response (i.e circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of Interfant 06) or
- Resistant disease (\> 30% blasts at end of induction treatment day 28-33) in subsequent morphological CR or
- High level bone marrow MRD (\> 1 in 1000) at week 12 ALL-BFM 2000/AIEOP BFM ALL 2009/EORTC 58951 protocols, week 12-15 of FRALLE A or at week 14 of UKALL2011
- Relapsed patients if at least one of the following criteria are met:
- Very early (\< 18 months from diagnosis) bone marrow or extramedullary relapse in second CR or
- Early (within 6 months of finishing therapy) isolated bone marrow relapse with bone marrow MRD \> 1 in 100 at day 35 of reinduction in second CR or
- Early (within 6 months of finishing therapy) bone marrow or combined relapse with high level bone marrow MRD (\> 1 in 1000) at the end of consolidation therapy (week 12-13 UKALL R3/INTREALL and COOPRALL protocols, prior to protocol M in BFM relapse protocol (ALL-REZ BFM 2002) and after Protocol II-IDA in AIEOP LLA Rec 2003)or
- Any relapse of infant or Philadelphia-positive ALL in morphological complete remission
- Any patient being transplanted in 3rd or greater CR
- These patients have a high (\> 50%) risk of relapse and will be monitored for evidence of MRD in bone marrow aspirates (monthly for months 1-6, 6 weekly months 7.5-12 post HSCT) for the first year post-transplant. Patients who become MRD +ve in the marrow at a level minimum 5 x 10-4 (or BCR-ABL/ABL ratio 0.05% in Ph+ve ALL patients with no IgH MRD marker) but are in morphological remission (\<5% blasts in BM) will be eligible to be treated pre-emptively with CD19ζ transduced CTL
- Prophylaxis arm
- Additionally, any patient (≤ 18 years) with ALL relapsing in the bone marrow (isolated or combined) after myeloablative allogeneic HSCT who achieves morphological remission after re-induction and who is a candidate for second HSCT at one of the participating centres is eligible to receive CD19ζ transduced CTL prophylactically
- Stem cell donors must be EBV sero-positive and HLA-matched (8/8 HLA A,B,C and DR at medium resolution typing) or a single antigenic/allelic (7/8) mismatch with the recipient
- A life expectancy of at least 12 weeks
- Karnofsky score of \>60% if \>10 years old or Lansky performance score of \>60 if ≤ 10 years old
- Patients must have transduced donor-derived EBV-specific CTLs with 15% or higher expression of CD19ζ determined by flow-cytometry which meet the specified release criteria
- Informed written consent indicating that patients are aware this is a research study and have been told of its possible benefits and toxic side effects
- Exclusion Criteria
- Patients with CD19 negative precursor B cell ALL
- EBV seronegative or \> single antigenic/allelic HLA-mismatched donor
- Active acute GVHD overall Grade 2 or higher or significant chronic GVHD requiring systemic steroids at the time of scheduled infusion of transduced CTL will be excluded until the patient is GVHD-free and off steroids
- Pre-existing severe lung disease (FEV1 or FVC \< 50% predicted) pre-HSCT or an oxygen requirement of \>28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for transduced CTL infusion
- Serum bilirubin \>3 times the upper limit of normal or an AST or ALT \> 5 times the upper limit of normal
- Serum creatinine \>3 times upper limit of normal
- Active severe intercurrent infection at the time of transduced CTL infusion (if present consult with Chief investigator).
- Patients in whom transduced donor-derived EBV-specific CTLs don't meet release criteria
- Serologically positive for Hepatitis B, C or HIV pre-HSCT
- Females of childbearing age with a positive pregnancy test
- Known allergy to DMSO
Exclusion
Key Trial Info
Start Date :
May 1 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 1 2015
Estimated Enrollment :
29 Patients enrolled
Trial Details
Trial ID
NCT01195480
Start Date
May 1 2012
End Date
November 1 2015
Last Update
May 17 2018
Active Locations (7)
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1
Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum
Essen, Germany, 45122
2
Hospital for Children and Adolescents III, Goethe University
Frankfurt, Germany, 60590
3
Medizinische Hochschule
Hanover, Germany, 30625
4
University Children's Hospital
Münster, Germany, 48149