Clinical Trials /

Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients

NCT02228096

Description:

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of an experimental therapy called CTL019 T-cells in pediatric patients with B-cell acute lymphoblastic leukemia, who are refractory to standard chemotherapy regimen or relapsed after allogeneic stem cell transplant

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients
  • Official Title: A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CCTL019B2205J
  • SECONDARY ID: 14BT022
  • NCT ID: NCT02228096

Conditions

  • B-cell Acute Lymphoblastic Leukemia
  • Relapsed B-cell Acute Lymphoblastic Leukemia
  • Refractory B-cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms

Purpose

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of an experimental therapy called CTL019 T-cells in pediatric patients with B-cell acute lymphoblastic leukemia, who are chemo-refractory, relapsed after allogeneic SCT, or are otherwise ineligible for allogeneic stem cell transplant.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
CTL019ExperimentalA dose of CTL019 transduced cells will consist of a single infusion of 2 to 5 x 10^6 CTL019 transduced cells/kg with a maximum dose of 2.5 x 10^8 CTL019 cells (non-weight adjusted).

    Eligibility Criteria

    Inclusion Criteria:

    - Relapsed or refractory pediatric B-cell ALL:

    1. 2nd or greater Bone Marrow (BM) relapse OR

    2. Any BM relapse after allogeneic SCT and must be > 6 months from SCT at the time of CTL019 infusion OR

    3. Refractory as defined by not achieving a CR (morphology <5% blasts) after 2 cycles of a standard chemotherapy regimen 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 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 (Calculated creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) > 60 mL/min/1.73 m2 OR serum creatinine based on age/gender;

    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 defined as ≤Grade 1 dyspnea and pulse oxygenation > 91% on room air

    5. Left Ventricular Shortening Fraction (LVSF) ≥ 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or MUGA

    - Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening

    - Life expectancy > 12 weeks

    - Age 2 at the time of initial diagnosis to age 21 at the time of initial diagnosis

    - Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening

    - Signed written informed consent and assent forms (if applicable) must be obtained prior to any study procedures

    - Once all other eligibility criteria are confirmed, must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. Note: Apheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received.

    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 [surface Immunoglobulin (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

    - Prior treatment with gene therapy product

    - Treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy

    - Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening

    - HIV infection at screening

    - Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)

    - 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: < 6 - 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, steroids [see above] rapamycin, thalidomide, or immunosuppressive antibodies such as rituximab anti-CD20 (rituximab), anti-TNF, anti-IL6, or anti-IL6R;

    4. Chemotherapy: i. 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 < 10 mg/m2/day, asparaginase; ii. The following drugs must be stopped > 4 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide), excluding the required lymphodepleting chemotherapy drugs;

    5. CNS disease prophylaxis: i. CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate).

    - Active CNS involvement by malignancy, defined as CNS-3 per National Comprehensive Cancer Network (NCCN) guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible12. Patient has participated in an investigational research study using an investigational agent within the last 30 days prior to screening

    - Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion

    - 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 contraception);

    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 participants on the study the vasectomized male partner should be the sole partner for that patient;

    4. BOTH of the following forms of contraception must be utilized: i. 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 contraception; ii. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;

    5. Use of intrauterine devices (IUDs) are excluded due to increased risks of infection and bleeding in this population; f). 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.

    6. 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 (i.e. have had no menses) 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: a. Demographics show age <11; b. Physical examination indicates Tanner Stage 1; c. Physician report/letter; d. Operative report or other source documentation in the patient record; e. Discharge summary; f. Follicle stimulating hormone measurement elevated into the menopausal range

    Maximum Eligible Age:21 Years
    Minimum Eligible Age:1 Year
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Response Rate
    Time Frame:12 months
    Safety Issue:
    Description:Overall Response Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and CSF. The primary endpoint will be based on the IRC assessment. The local investigator's assessed results will be used for sensitivity analysis.

    Secondary Outcome Measures

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Novartis Pharmaceuticals

    Trial Keywords

      Last Updated

      March 14, 2017