Paediatric relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia MedDRA version: 21.0 Level: LLT Classification code 10060390 Term: Leukaemia lymphoblastic acute System Organ Class: 100000004864
Conditions
Sponsors
Institut de Recherches Internationales Servier (I.R.I.S)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 2a. Age ranging from birth to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 34 Patients unwilling to undergo a safety follow-up for 15 years 10a Previous treatment with gene or gene-modified cell therapy medicine products (except autologous CD19 CAR-T cell therapy) 61 Known history of CRS grade 4 related to previous CAR T cell therapy 11a Use of previous anti-leukemic therapy (including approved therapies and other investigational products) within 5 half-lives prior to UCART 19 administration. Inotuzumab ozogamicin must be stopped at least 28 days prior to UCART19 administration. Participation in noninterventional registries or epidemiological studies is allowed 12 CD19-negative B-cell leukaemia 15 Burkitt cell acute leukaemia (L3 ALL) 45a Clinically suspected extramedullary involvement (except CNS and isolated skin involvement) 37a Evidence of disease progression after cytoreduction, if administered 17a Active CNS leukemia 28 Clinically active significant CNS dysfunction 29a Known history of irreversible severe neurological toxicity related to previous antileukemic treatment leading to organic central nervous system lesions 30 Primary immunodeficiency or bone marrow failure syndrome 14 Weight 6 weeks prior to Screening 31 Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) prior to Inclusion 18 Use of rituximab and other anti CD20 antibodies known to have the same epitope as rituximab or anti CD20 for which the epitope is unknown within 3 months prior to UCART19 infusion 19 Presence of donor-specific anti-HLA antibodies directed against UCART19 20b Active, acute or chronic graft versus host disease (GvHD) requiring systemic treatment within 4 weeks of UCART19 infusion 21a Patients with autoimmune disease requiring systemic immunosuppression that cannot be stopped 22 A known hypersensitivity to any of the test materials or related compounds including murine and bovine products 24 Active systemic bacterial, fungal, protozoal or viral infection not controlled by adequate treatment, and presence of positive blood cultures within 7 days before Inclusion 33 Patients tested positive for human immunodeficiency virus (HIV) and/or or human T-lymphotropic virus (HTLV) 25a Abnormal findings during the screening period, any other medical condition(s) or laboratory findings that in the opinion of the investigator, might jeopardize the patient's safety 27a Risk of pregnancy or non compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 7 days prior to inclusion. Within the frame of this study, female participants of childbearing potential and male participants with partners of childbearing potential must use an effective method of birth control, as well as their partners, from the screening period up to 12 months after the last dose of Investigational Medicinal Product (IMP) administration 36a Any known contraindication to any of the drugs that will be used for the lymphodepletion (fludarabine, cyclophosphamide, alemtuzumab) or other drugs proposed for safety issues (including tocilizumab, rituximab) 59a Systemic corticosteroids within 5 days before administration of UCART19. However, premedication related to Alemtuzumab administration or physiological replacement doses (<12 mg/m2/day hydrocortisone or equivalent) are allowed 62 In addition to contraindications reported
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of UCART19 in paediatric patients with relapsed or refractory B-ALL.;Secondary Objective: To determine the ability of UCART19 to achieve molecular remission at D28 after the first UCART19 infusion;Primary end point(s): - Adverse events graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE) version V4.3 June 14, 2010, throughout the study, except CRS, TLS and acute GvHD events that will be graded according to the grading systems of Lee, Cairo and Harris, respectively ; - Clinical examination and cardiac evaluation (ECG, echocardiography) ; - Vital signs (blood pressure, heart rate, body temperature, respiratory rate, oxygen saturation level), - Laboratory data assessments: haematology, biochemistry, coagulation parameters ; - Viral / bacterial / protozoal infection monitoring,;Timepoint(s) of evaluation of this end point: safety will be evaluated on an on-going basis throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- The activity of UCART19 will include a careful examination and valuation of the blood and the marrow if indicated. 2- MRD evaluation by multiparameter flow cytometry and/or qPCR;Timepoint(s) of evaluation of this end point: 1: Day 28 after the first UCART19 infusion 2: During the screening period, at D-1, (D14), D28, D56, D84, M4, M6, M9, M12 | — |
Countries
Belgium, France, Spain, United Kingdom, United States
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed