- Relapsed or refractory pediatric B-cell ALL.
1. 2nd or greater Bone Marrow (BM) relapse OR.
2. Any BM relapse after allogeneic stem cell transplantation (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 therapy
(TKI), or if TKI therapy is contraindicated OR.
5. Ineligible for allogeneic SCT.
- For relapsed patients, documentation of CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study entry.
- Adequate organ function defined as:
1. 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.
2. Alanine Aminotransferase (ALT) 5 times the upper limit of normal (ULN) for
3. Bilirubin < 2.0 mg/dL.
4. Must have a minimum level of pulmonary reserve as Grade 1 dyspnea and pulse
oxygenation > 91% on room air.
5. 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).
- Bone marrow with 5% lymphoblasts by morphologic assessment at screening.
- Life expectancy > 12 weeks.
- Age 3 at the time of screening to age 21 at the time of initial diagnosis
- Karnofsky (age 16 years) or Lansky (age < 16 years) performance status 50 at
- Must have an apheresis product of non-mobilized cells received and accepted by the
- Isolated extra-medullary disease relapse
- Patients with concomitant genetic syndrome: 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.
- 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)
- Prior malignancy, except carcinoma in situ of the skin or cervix treated with
curative intent and with no evidence of active disease
- Treatment with any prior gene therapy product
- Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
- Active or latent hepatitis B or active hepatitis C (test within 8 weeks of
screening), or any uncontrolled infection at screening
- Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).
- Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.
- Patient has an investigational medicinal product within the last 30 days prior to
- Pregnant or nursing women.
- Women of child-bearing potential (defined as all women physiologically capable of
becoming pregnant) and all male participants, unless they are using highly effective
methods of contraception for a period of 1 year after the CTL019 infusion. Highly
effective contraception methods include:
1. Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are NOT acceptable methods of
2. Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study
treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
3. Male sterilization (at least 6 months prior to screening). For female patients
on the study the vasectomized male partner should be the sole partner for that
4. BOTH of the following forms of contraception must be utilized:
- Use of oral, injected or implanted hormonal methods of contraception or
other forms of hormonal contraception that have comparable efficacy
(failure rate <1%), for example hormone vaginal ring or transdermal hormone
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
5. Use of IUDs are excluded due to increased risks of infection and bleeding in
6. In case of use of oral contraception, women must be stable on the same pill for
a minimum of 3 months before taking study treatment.
Women who are not of reproductive potential (defined as either <11 years of age,
Tanner Stage 1, post-menopausal for at least 24 consecutive months or have
undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy) are
eligible without requiring the use of contraception. Acceptable documentation
includes written or oral documentation communicated by clinician or clinician's
staff of one of the following:
1. Demographics show age <11
2. Physical examination indicates Tanner Stage 1
3. Physician report/letter
4. Operative report or other source documentation in the patient record
5. Discharge summary
6. Follicle stimulating hormone measurement elevated into the menopausal range
- The following medications are excluded:
1. Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to
CTL019 infusion. However, the following physiological replacement doses of
steroids are allowed:
< 12 mg/m2/day hydrocortisone or equivalent
2. Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be
completed > 6 weeks prior to CTL019 infusion
3. GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CTL019
infusion (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs,
mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as
anti-CD20 (rituximab), anti-TNF, anti-IL6 or anti-IL6R)
The following drugs must be stopped > 1 week prior to CTL019 infusion and should
not be administered concomitantly or following lymphodepleting chemotherapy:
hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25
mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non-pegylated)
The following drugs must be stopped >2 weeks prior to CTL019 infusion:
salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2,
anthracyclines, cyclophosphamide), excluding the required lymphodepleting
chemotherapy drugs Pegylated-asparaginase must be stopped > 4 weeks prior to
5. CNS disease prophylaxis:
CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion
(e.g. intrathecal methotrexate)
- Anti T-cell therapy: Administration of any T cell or toxic agent is strongly
discouraged since residual lytic levels may destroy the infused CTL019 cell or
prevent their in vivo expansion.
Other protocol-defined inclusion/exclusion may apply.
Minimum Eligible Age: 3 Years
Maximum Eligible Age: 33 Years
Eligible Gender: Both