Trial Search Results

Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL

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.

Stanford is currently not 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:

   - 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 age.

      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
   screening.

   - Must have an apheresis product of non-mobilized cells received and accepted by the
   manufacturing site.

Exclusion Criteria:

   - 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 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.

   - 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)

      4. Chemotherapy:

      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
      CTL019 infusion

      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.

Ages Eligible for Study

3 Years - 30 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

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