E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia |
|
E.1.1.1 | Medical condition in easily understood language |
Children with B-cell lymphoblastic leukaemia that has relapsed or for whom previous treatment has not worked. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060390 |
E.1.2 | Term | Leukaemia lymphoblastic acute |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of UCART19 in paediatric patients with relapsed or refractory B-ALL. |
|
E.2.2 | Secondary objectives of the trial |
To determine the ability of UCART19 to achieve molecular remission at D28. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients
2. Age ranging between 6 months and <18years
3. Patients with relapsed or refractory CD19-positive B-acute lymphoblastic leukemia (B-ALL) (National Comprehensive Cancer Network (NCCN), 2015),
- Morphologically confirmed
- 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 available treatment options
- Eligible for allogeneic hematopoietic stem cells transplantation with suitable donor available
4. Estimated life expectancy ≥ 12 weeks (according to investigator’s judgement)
5. Considered medically fit for allo-HSCT
6. Eastern Cooperative Oncology Group ECOG performance status < 2
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 |
|
E.4 | Principal exclusion criteria |
9. Foreseeable poor compliance to the study procedures
10. Previous treatment with investigational gene or cell therapy medicine products. Prior treatment with blinatumomab is allowed
11. Use of other investigational products or previous chemotherapy including biologic/targeted therapy or immunological agents within 5 half-lives or within 14 days prior to UCART 19 administration, whichever has a
shorter duration
12. CD19-negative B-cell leukaemia
13. Absence of suitable HLA matched or mismatched donor
14. Weight< 8.8 kgs
15. Burkitt cell acute leukaemia (L3 ALL)
16. Autologous HSCT within 6 weeks or allogeneic HSCT within 3 months prior Inclusion
17. Uncontrolled CNS leukemia
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
20. Active, acute or chronic GvHD requiring therapy
21. Patients currently treated with immunosuppressive agents that cannot be stopped (e.g., GvHD or autoimmune disease)
22. A known hypersensitivity to any of the test materials or related compounds including murine and bovine products
23. Unstable cardiovascular disease,
24. Active bacterial, fungal, protozoal or viral infection not controlled by adequate treatment, and presence of positive blood cultures within 7 days before Inclusion
25. Abnormal findings during the screening period, any other medical condition(s) or laboratory findings that in the opinion of the investigator renders the patient unsuitable for subsequent allo-HSCT.
26. Any planned medical/surgical treatment that might interfere with the ability to comply with the study requirements
27. 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 for a duration of 12 months after Investigational Medicinal Product (IMP) administration.
32. Evidence of other malignancy within 2 years prior to Inclusion (except in situ basal or squamous cervix or skin cell carcinoma) |
|
E.5 End points |
E.5.1 | 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, 2016), respectively ;
- Clinical examination and cardiac evaluation (ECG, echocardiography) ;
- Vital signs (blood pressure, heart rate, body temperature, respiratory rate, oxygen saturation),
- Laboratory data assessments: haematology, biochemistry, coagulation parameters ;
- Lung function test, oxygen saturation level ;
- Lumbar puncture ;
- Viral / bacterial / protozoal infection monitoring, |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
safety will be evaluated on an on-going basis throughout the trial |
|
E.5.2 | 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-Disease response including molecular (CRm), complete or incomplete response (CR/CRi), partial remission (PR), progressive disease, stable disease, treatment failure, time to progression, progression-free survival and overall survival, relapse, refractory disease will be recorded. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Day 28.
2: During the treatment period (D28, D56 and D84) or ahead of allo-HSCT conditioning regimen initiation. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Analysis of safety and/or efficacy biomarkers |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |