A clinical study to provide the opportunity to be treated with CTL019, an investigational gene therapy, for children and adolescent patients with a recurrent form of B-cell acute lymphoblastic leukaemia after the closure of the Novartis single-arm phase II pivotal registration trial (Study CCTL019B2202) and to collect additional safety information.

Phase 1

Conditions: Paediatric/young adult patients with B-cell acute lymphoblastic leukaemia who are chemo-refractory, relapsed after allogeneic SCT, or are otherwise ineligible for allogeneic SCT.
MedDRA version: 21.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864
MedDRA version: 21.0Level: LLTClassification code 10063621Term: Acute lymphoblastic leukaemia recurrentSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-001991-31-NO

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

Patients eligible for inclusion in this program have to meet all of the following criteria:
1. Relapsed or refractory B-cell ALL in pediatric or young adult patients
2. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry with adequate organ function.
3. Adequate organ function as defined in the protocol.
4. Life expectancy > 12 weeks.
5. Age < 26 years of age at the time of Screening.
6. Karnofsky (age = 16 years) or Lansky (age < 16 years) performance status = 50 at Screening.
7. Patients previously treated with blinatumomab who have detectable leukemia and documented CD19+ expression (via flow cytometry) and confirmed absence of CD19- leukemic blasts at Screening may be included.
8. Signed written informed consent form (ICF) and assent form if applicable must be obtained prior to any study procedures
9. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, stored leukapheresis product.
10. Once all other eligibility criteria are confirmed, must have a leukapheresis product of nonmobilized cells received and accepted by
the manufacturing site. Note: Leukapheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received.
11. Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria:
1. Isolated extra-medullary disease relapse.
2. Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
3. Patients with Burkitt's lymphoma/leukemia.
4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
5. Prior treatment with any gene therapy product.
6. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab who fulfill inclusion criterion no. 8.
7. Presence of active replication of hepatitis B or hepatitis C (for detailed criteria see Appendix 2 of main protocol). Serology must be repeated, if the interval between testing at Screening and CTL019 infusion exceeds 8 weeks.
8. HIV positivity as indicated by serology. Serology must be repeated, if the interval between testing at Screening and CTL019 infusion exceeds 8 weeks.
9. Presence of grade 2 to 4 acute or extensive chronic graft versus host disease (GVHD).
10. Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening.
11. Previous or concurrent malignancy (exceptions defined in the protocol)
12. Intolerance to the excipients of the CTL019 cell product (i.e. dimethyl sulfoxide).
13. Cardiac or cardiac repolarization abnormality.
14. Patients enrolled in this study are not permitted to participate in additional parallel investigational drug or device studies.
15. Patient has an investigational medicinal product within the last 30 days prior to screening.
16. The following medications are excluded:
a. Steroids,
b. Allogeneic cellular therapy,
c. GVHD therapies,
d. Chemotherapy,
e. CNS disease prophylaxis,
f. Radiotherapy,
g. Anti-T cell antibodies.
17. Pregnant or nursing (lactating) women.
18. Women of child-bearing potential
19. Sexually active males must use a condom during intercourse from enrollment and for at least 12 months after the CTL019 infusion and until CAR T cells are no longer present by qPCR on 2 consecutive tests.
Other protocol-defined exclusion criteria may apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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