A study to evaluate the safety and efficacy of UCART19 in children with B cell lymphoblastic leukaemia that has relapsed or not responded to other treatments
- Conditions
- Paediatric relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemiaMedDRA version: 21.0Level: LLTClassification code 10060390Term: Leukaemia lymphoblastic acuteSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004293-15-GB
- Lead Sponsor
- Institut de Recherches Internationales Servier (I.R.I.S)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
1. Male or female patients
2a. Age ranging from birth to <18 years
3b. Patients with relapsed or refractory CD19-positive B-acute lymphoblastic leukemia (B-ALL) (National Comprehensive Cancer Network (NCCN), 2020),
- Morphologically confirmed with = 5% leukemic blasts in the bone marrow
- or presenting a quantifiable MRD load of 1x10-3 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) at the end of the last induction treatment
- Who have exhausted alternative treatment options
Relapsed disease is defined as:
- second or subsequent bone marrow relapse or,
- any bone marrow relapse after allo-SCT.
Refractory disease is defined by not achieving an initial complete response (CR) after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemo-refractory
Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated.
4. Estimated life expectancy = 12 weeks (according to investigator’s judgement)
6a. Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age = 16 years at the time of assent/consent) performance status = 50
35b. Adequate organ function defined as:
a. Creatinine clearance = 30 mL/min (as calculated using the method standard for the institution). In equivocal
cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately.
b. Serum ALT/AST = 5 x ULN
c. Total bilirubin = 1.5 x ULN (unless the patient has a history of Gilbert’s Syndrome, in which case, total bilirubin must be = 2.5 ULN)
d. Left Ventricular Ejection Fraction (LVEF) = 45% and no clinically significant ECG findings
44. Availability of a donor for potential allo-HSCT in the event of persistent marrow aplasia without evidence of residual leukemia
7. Written informed consent from parent(s) or legal representative and or written assent from patient when applicable obtained prior any study-specific procedure of the protocol
60a. Patients previously treated with autologous CAR T-cells must show no detectable CAR-T cells in blood, as demonstrated by: presence of CD19+ cells (CD19+ B-cell count = 50cells/µL in peripheral blood and/or = 1% CD19+ hematogones in bone marrow) or by qPCR (if available for clinical use) showing an absence of CAR transgene
Are the trial subjects under 18? yes
Number of subjects for this age range: 18
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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< 8.8 kgs
16b Allogeneic HSCT within 3 months prior to screening; any donor lymphocyte infusions must be completed > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 ;<br><br>- Clinical examination and cardiac evaluation (ECG, echocardiography) ;<br><br>- Vital signs (blood pressure, heart rate, body temperature, respiratory rate, oxygen saturation level),<br><br>- Laboratory data assessments: haematology, biochemistry, coagulation parameters ;<br><br>- 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 Outcome Measures
Name Time Method Secondary end point(s): 1- The activity of UCART19 will include a careful examination and valuation of the blood and the marrow if indicated.<br>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<br>2: During the screening period, at D-1, (D14), D28, D56, D84, M4, M6, M9, M12