A clinical study to provide the opportunity to be treated with CTL019, an investigational gene therapy, for children and adolescent patients with arecurrent 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-IT
• Lead Sponsor: OVARTIS PHARMA AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2020-10-13
• Study Start: 2021-05-24
• Last Update Posted: 21 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 74

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:
a. Second or greater bone marrow relapse, OR
b. Any bone marrow relapse after allogeneic SCT and must be = 6
months from SCT at the time of CTL019 infusion, OR
c. Primary refractory as defined by not achieving a CR after 2 cycles of a
standard chemotherapy regimen or chemorefractory as defined by not
achieving a CR after 1 cycle of standard chemotherapy for relapsed
leukemia, OR
d. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible
if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor
(TKI) therapy, or if TKI therapy is contraindicated, OR
e. Ineligible for allogeneic SCT because of:
- Comorbid disease,
- Other contraindications to allogeneic SCT conditioning regimen,
- Lack of suitable donor,
- Prior SCT,
- Declines allogeneic SCT as a therapeutic option after documented
discussion about the role of SCT with a bone marrow transplantation
physician who is not a member of the CTL019 study team.
2. For relapsed patients, CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study
entry. For relapsed or refractory patients previously treated with
blinatumomab, CD19 tumor expression must be demonstrated (via flow
cytometry) at Screening.
3. Adequate organ function defined as:
a. Renal function defined as: A serum creatinine based on age/gender as
follows: Maximum Serum Creatinine (mg/dL) - Age/Male/Female: 1 to <
2 years/0.6/0.6; 2 to < 6 years/0.8/0.8; 6 to < 10 years/1.0/1.0; 10 to
< 13 years/1.2/1.2; 13 to < 16 years/1.5/ 1.4; = 16 years/1.7/1.4.
b. Alanine Aminotransferase (ALT) = 5 times the upper limit of normal
(ULN) for age.
c. Bilirubin < 2.0 mg/dL.
d. Must have a minimum level of pulmonary reserve defined as = Grade 1
dyspnea and pulse oxygenation > 91% on room air.
e. Left Ventricular Shortening Fraction (LVSF) = 28% confirmed by
echocardiogram (ECHO), or Left Ventricular Ejection Fraction (LVEF) =
45% confirmed by echocardiogram or Multiple Uptake Gated Acquisition
(MUGA) within 7 days of screening.
4. Bone marrow with = 5% lymphoblasts by morphologic assessment at
screening.
5. Life expectancy > 12 weeks.
6. Age < 26 years of age at the time of Screening.
7. Karnofsky (age = 16 years) or Lansky (age < 16 years) performance
status = 50 at screening.
8. 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. In this case, at least 1-week washout period must be applied
from last dose of blinatumomab to start of leukapheresis. Patients
previously treated with blinatumomab with no detectable MRD (i.e. MRD
negative demonstrated by leukemic blasts < 0.01%) will be excluded.
Note: blinatumomab must not be administered as a bridging therapy
prior to CTL019 infusion while the patient is awaiting manufacture of
CTL019
9. Signed written informed consent and assent forms if applicable must
be obtained prior to any study procedures.
10. Must meet the institutional criteria to undergo leukapheresis or have
an acceptable, stored leukapheresis product.
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

Exclusion Criteria

1. Isolated extra-medullary disease relapse.
2. Patients with concomitant genetic syndromes.
3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation).
4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
5. Treatment with any prior 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.
10. Active CNS involvement by malignancy.
11. Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening.
12. Previous or concurrent malignancy with the following exceptions:
a. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry).
b. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study.
c. A primary malignancy which has been completely resected and in CR for = 5 years.
13. Intolerance to the excipients of the CTL019 cell product (i.e. dimethyl sulfoxide).
14. Cardiac or cardiac repolarization abnormality.
15. Patients enrolled in this study are not permitted to participate in additional parallel investigational drug or device studies.
16. Patient has an investigational medicinal product within the last 30 days prior to screening.
17. Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
18. Pregnant or nursing (lactating) women.
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.
20. Sexually active males must use a condom during intercourse while taking study treatment 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