This is a single arm, open-label, multi-center, phase II study to determine the efficacy and
safety of CTL019 in pediatric patients with r/r B-cell ALL and high risk B-cell ALL at first
relapse. Determine feasibility and safety of CTL019 therapy in pediatric patients with high
risk B-cell ALL that relapsed < 6 months post allo-HSCT.
This is a three Cohort, open-label, multi-center, phase II study to determine the efficacy
and safety of CTL019 in pediatric patients with r/r B-cell ALL (Main Cohort closed for an
enrollment), high risk B-cell ALL patients at first relapse (Cohort 1 open for an
enrollment), and feasibility and safety of CTL019 in high risk B-cell ALL patients that
relapsed <6 months post allo-HSCT (Cohort 2 is open for an enrollment).
The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product
Preparation & Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary
Follow-up (if applicable) and Survival Follow-up. The total duration of the study is 5 years
from CTL019 cell infusion.
Inclusion Criteria (Main Cohort closed for an enrollment):
- 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.
- 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
- Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.
Exclusion Criteria (Main Cohort closed for an enrollment):
- 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
therapy
- 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
screening.
- Pregnant or nursing (lactating) women.
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they agree to use highly effective methods of contraception
from signing informed consent and through at least 12 months after the CTL019 infusion
- Sexually active males must use a condom during intercourse from signing informed
consent to at least 12 months after the CTL019 infusion
Inclusion Criteria (Cohort 1 open for an enrollment):
a. B-cell acute lymphoblastic leukemia and:
- First relapse AND hypodiploid cytogenetics: fewer than 44 chromosomes and/or DNA index
< 0.81, or other clear evidence of a hypodiploid clone OR
- First relapse AND t(17;19) with defined TCF3-HLF fusion OR
- First relapse with any cytogenetics provided the relapse occurred ≤ 36 months of
initial diagnosis AND MRD at end of reinduction therapy is ≥0.01% by flow cytometry
(local assessment)
- For relapsed patients, documentation of CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study entry.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- Life expectancy > 12 weeks.
- Age up to 25 years at the time of screening.
- Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.
Exclusion Criteria (Cohort 1 , open for an enrollment):
- 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
therapy
- 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
screening.
- Pregnant of nursing (lactating) women.
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they agree to use highly effective methods of contraception
from signing informed consent and through at least 12 months after the CTL019 infusion
- Sexually active males must use a condom during intercourse from signing informed
consent to at least 12 months after the CTL019 infusion
Inclusion Criteria (Cohort 2 open for an enrollment):
a. B-cell acute lymphoblastic leukemia and:
- Any BM relapse after allogeneic stem cell transplantation (allo-HSCT) and must be < 6
months from HSCT at the time of CTL019 infusion
- For relapsed patients, documentation of CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study entry.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- Life expectancy > 12 weeks.
- Age up to 25 years at the time of screening.
- Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.
Exclusion Criteria (Cohort 2 , open for an enrollment):
- 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
therapy
- 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
screening.
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they agree to use highly effective methods of contraception
from signing informed consent and through at least 12 months after the CTL019 infusion
- Sexually active males must use a condom during intercourse from signing informed
consent to at least 12 months after the CTL019 infusion
Other protocol-defined inclusion/exclusion may apply.
