Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
University College, London
With
European Union
The Leukemia and Lymphoma Society
Children with Leukaemia
Department of Health, United Kingdom
JP Moulton Charitable Foundation
Deutsche Krebshilfe e.V., Bonn (Germany)
Age
0–18
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
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
You may not be if
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).
