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Brief Title

Phase III B in Acute Lymphoblastic Leukemia

Official Title

Phase IIIb Study for Relapsed/Refractory Pediatric/Young Adult Acute Lymphoblastic Leukemia Patients to be Treated With CTL019

Brief Summary

      This is a single arm, open-label, multi-center, phase III B study to determine the safety and
      efficacy of CTL019 in pediatric/young adult patients with r/r B-cell ALL.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Number of participants with Adverse Events (AEs)

Secondary Outcome

 Complete Remission (CR)

Condition

Acute Lymphoblastic Leukemia

Intervention

CTL019

Study Arms / Comparison Groups

 CTL019 - traetment arm
Description:  all enrolled subjects will get the study treatment.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

69

Start Date

April 24, 2017

Completion Date

December 30, 2020

Primary Completion Date

August 21, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Relapsed or refractory B-cell ALL in pediatric or young adult patients:

               1. Second or greater bone marrow relapse OR

               2. Any bone marrow relapse after allogeneic 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 (TKI) therapy,
                  or if TKI therapy is contraindicated OR

               5. Ineligible for allogeneic SCT

          2. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral
             blood by flow cytometry within 3 months of program entry

          3. Adequate organ function defined as:

               1. A serum creatinine based on age/gender as follows: Maximum Serum Creatinine
                  (mg/dL). Age Male Female: to < 2 years 0.6 0.6; 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. ALT ≤ 5 times the upper limit of normal (ULN) for age.

               3. Bilirubin < 2.0 mg/dL.

               4. Minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse
                  oxygenation > 91% on room air.

               5. Left Ventricular Shortening Fraction ≥ 28% by echocardiogram, or Left Ventricular
                  Ejection Fraction ≥ 45% by echocardiogram or Multiple Uptake Gated Acquisition
                  (MUGA).

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

          5. Life expectancy > 12 weeks.

          6. Age 3 years at the time of screening to age 21 years at the time of initial diagnosis.

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

          8. Patients previously treated with blinatumomab who have detectable leukemia and
             documented CD19+ expression (via flow cytometry) and confirmed absence of CD19-
             leukemic blasts at Screening may be included. In this case, at least 1 week washout
             period must be applied from last dose of blinatumomab to start of leukapheresis.
             Patients previously treated with blinatumomab with no detectable MRD (i.e. MRD
             negative demonstrated by leukemic blasts < 0.01%) will be excluded.

          9. Must have a leukapheresis product of non-mobilized cells received and accepted by the
             manufacturing site.

        Exclusion criteria

          1. Isolated extra-medullary disease relapse.

          2. Concomitant genetic syndromes associated with bone marrow failure states: Fanconi
             anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure
             syndrome. Patients with Down Syndrome will not be excluded.

          3. 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).

          4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
             intent and with no evidence of active disease.

          5. Prior treatment with any gene therapy product.

          6. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy,
             except for patients pre-treated with blinatumomab

          7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),
             or any uncontrolled infection at screening

          8. Human immunodeficiency virus (HIV) positive test within 8 weeks of screening.

          9. Presence of grade 2 to 4 acute or extensive chronic GVHD.

         10. Uncontrolled acute life threatening bacterial, viral or fungal infection atScreening

         11. Active central nervous system involvement by malignancy, defined as CNS-3 per NCCN
             guidelines.

         12. Investigational medicinal product within the last 30 days prior to screening.

        12. Pregnant or nursing women. 13. Women of child-bearing potential and all male
        participants, unless they are using highly effective methods of contraception for a period
        of 1 year after the CTL019 infusion.

        14. The following medications are excluded:

          1. Steroids: Therapeutic systemic doses of steroids must be stopped > 72 hours prior to
             CTL019 infusion.

          2. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed > 6
             weeks prior to CTL019 infusion.

          3. GVHD therapies: Any systemic drug used for GVHD must be stopped > 4 weeks prior to
             CTL019 infusion to confirm that GVHD recurrence is not observed.

          4. Chemotherapy:

               -  TKIs and hydroxyurea must be stopped > 72 hours prior to CTL019 infusion.

               -  must be stopped > 1 week prior to CTL019 infusion: vincristine, 6-mercaptopurine,
                  6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day,
                  asparaginase (non pegylated).

               -  must be stopped > 2 weeks prior to CTL019 infusion: salvage chemotherapy (e.g.
                  clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide,
                  methotrexate ≥ 25 mg/m2).

               -  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).

          6. Radiotherapy

               -  Non-CNS site of radiation must be completed > 2 weeks prior to CTL019 infusion.

               -  CNS directed radiation must be completed > 8 weeks prior to CTL019 infusion.

          7. Anti T-cell antibodies: Administration of any T cell lytic or toxic antibody (e.g.
             alemtuzumab) within 8 weeks prior to CTL019 is prohibited Other protocol-defined
             inclusion/exclusion may apply
      

Gender

All

Ages

N/A - 25 Years

Accepts Healthy Volunteers

No

Contacts

Novartis Pharmaceuticals, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT03123939

Organization ID

CCTL019B2001X

Secondary IDs

2016-001991-31

Responsible Party

Sponsor

Study Sponsor

Novartis Pharmaceuticals


Study Sponsor

Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals


Verification Date

February 2020