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

Phase 1

Active, not recruiting

• Conditions: Paediatric relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia; MedDRA version: 20.0Level: LLTClassification code 10060390Term: Leukaemia lymphoblastic acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004293-15-ES
• Lead Sponsor: Institut de Recherches Internationales Servier (I.R.I.S)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-17
• Last Update Posted: 19 April 2021

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Male or female patients

2. Age ranging between 6 months and <18 years

3a. Patients with relapsed or refractory CD19-positive B-acute lymphoblastic leukemia (B-ALL) (National Comprehensive Cancer Network (NCCN), 2017),
- 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

35.a 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 = 3 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
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

Exclusion Criteria

34. Patients unwilling to undergo a safety follow-up for 15 years

9. Foreseeable poor compliance to the study procedures

10. Previous treatment with gene or gene-modified cell therapy medicine products. Prior treatment with blinatumomab is allowed

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 non-interventional 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

29. Known history of severe neurological toxicity related to blinatumomab

30. Primary immunodeficiency or bone marrow failure syndrome

14. Weight< 8.8 kgs

16a. Allogeneic HSCT within 6 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

20a. Active, acute or chronic GvHD requiring systemic use therapy

21. Patients currently treated with immunosuppressive agents 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

26. Any planned medical/surgical treatment that might interfere with the ability to comply with the study requirements

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).

ELIGIBILITY CRITERIA FOR UCART19 ADMINISTRATION (WITHIN 24 HOURS PRIOR TO INFUSION)

38a. Adequate organ functions including renal and hepatic function based on the last assessment performed within the lymphodepletion period, defined as:
- Creatinine clearance = 30 mL/min (as calculated using th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified