This is a single arm, open-label, multi-center, phase III B study to determine the safety and
efficacy of CTL019 in pediatric/young adult patients with r/r B-cell ALL.
1. Relapsed or refractory B-cell ALL in pediatric or young adult patients:
1. Second or greater bone marrow relapse OR
2. Any bone marrow relapse after allogeneic SCT and must be ≥ 6 months from SCT at
the time of CTL019 infusion OR
3. 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
4. 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
5. Ineligible for allogeneic SCT
2. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral
blood by flow cytometry within 3 months of program entry
3. Adequate organ function defined as:
1. A serum creatinine based on age/gender as follows: Maximum Serum Creatinine
(mg/dL). Age Male Female: to < 2 years 0.6 0.6; 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
2. ALT ≤ 5 times the upper limit of normal (ULN) for age.
3. Bilirubin < 2.0 mg/dL.
4. Minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse
oxygenation > 91% on room air.
5. Left Ventricular Shortening Fraction ≥ 28% by echocardiogram, or Left Ventricular
Ejection Fraction ≥ 45% by echocardiogram or Multiple Uptake Gated Acquisition
4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
5. Life expectancy > 12 weeks.
6. Age 3 years at the time of screening to age 21 years at the time of initial diagnosis.
7. Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50 at
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.
9. Must have a leukapheresis product of non-mobilized cells received and accepted by the
1. Isolated extra-medullary disease relapse.
2. Concomitant genetic syndromes associated with bone marrow failure states: 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 (i.e. patients with mature B-cell ALL,
leukemia with B-cell surface immunoglobulin (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. 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
7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),
or any uncontrolled infection at screening
8. Human immunodeficiency virus (HIV) positive test within 8 weeks of screening.
9. Presence of grade 2 to 4 acute or extensive chronic GVHD.
10. Uncontrolled acute life threatening bacterial, viral or fungal infection atScreening
11. Active central nervous system involvement by malignancy, defined as CNS-3 per NCCN
12. Investigational medicinal product within the last 30 days prior to screening.
12. Pregnant or nursing women. 13. Women of child-bearing potential and all male
participants, unless they are using highly effective methods of contraception for a period
of 1 year after the CTL019 infusion.
14. The following medications are excluded:
1. Steroids: Therapeutic systemic doses of steroids must be stopped > 72 hours prior to
2. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed > 6
weeks prior to CTL019 infusion.
3. GVHD therapies: Any systemic drug used for GVHD must be stopped > 4 weeks prior to
CTL019 infusion to confirm that GVHD recurrence is not observed.
- TKIs and hydroxyurea must be stopped > 72 hours prior to CTL019 infusion.
- must be stopped > 1 week prior to CTL019 infusion: vincristine, 6-mercaptopurine,
6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day,
asparaginase (non pegylated).
- must be stopped > 2 weeks prior to CTL019 infusion: salvage chemotherapy (e.g.
clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide,
methotrexate ≥ 25 mg/m2).
- Pegylated-asparaginase must be stopped > 4 weeks prior to CTL019 infusion.
5. CNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to
CTL019 infusion (e.g. intrathecal methotrexate).
- Non-CNS site of radiation must be completed > 2 weeks prior to CTL019 infusion.
- CNS directed radiation must be completed > 8 weeks prior to CTL019 infusion.
7. Anti T-cell antibodies: Administration of any T cell lytic or toxic antibody (e.g.
alemtuzumab) within 8 weeks prior to CTL019 is prohibited Other protocol-defined
inclusion/exclusion may apply