Trial Search Results

Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory 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 All-HSCT.

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Novartis Pharmaceuticals

Stanford Investigator(s):

Intervention(s):

  • Biological: Single dose of CTL019

Phase:

Phase 2

Eligibility


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.

Ages Eligible for Study

N/A - 25 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office
650-498-7061
Not Recruiting