Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients (JULIET)

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma (DLBCL) focused on measuring Diffuse large B-cell lymphoma,, DLBCL,, Relapsed/refractory,, CTL019, CART19, CART, CAR T cells, Chimeric antigen receptor Read More

Inclusion Criteria:

• Written informed consent must be obtained prior to any screening procedures

• Histologically confirmed DLBCL at last relapse(by central pathology review before enrolment.

  .- Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT

• Measurable disease at time of enrollment
• Life expectancy ≥12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening

• Adequate organ function:

  • Renal function defined as:

    • A serum creatinine of ≤1.5 x Upper Limit of Normal ULN OR
    • Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m2

  • Liver function defined as:

    • Alanine Aminotransferase (ALT) ≤ 5 times the Upper Limit of Normal (ULN) for age
    • Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air
  • Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)

  • Adequate bone marrow reserve without transfusions defined as:

    • Absolute neutrophil count (ANC) > 1.000/mm3
    • Absolute lymphocyte count (ALC) ≥ 300/mm3
    • Platelets ≥ 50.000//mm3
    • Hemoglobin > 8.0 g/dl
  • Must have an apheresis product of non-mobilized cells accepted for manufacturing
  • Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for at least 12 months following CTL019 infusion and until CAR T cells are no longer present by PCR on two consecutive tests

Exclusion Criteria:

• Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
• Treatment with any prior gene therapy product
• Active Central Nervous System (CNS) involvement by malignancy
• Prior allogeneic HSCT
• Eligible for and consenting to ASCT
• Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
• Investigational medicinal product within the last 30 days prior to screening

• The following medications are excluded:

  • 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
  • Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks prior to enrollment
  • Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of infusion
  • Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer
  • CNS disease prophylaxis must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
• Prior radiation therapy within 2 weeks of infusion
• Active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive )
• HIV positive patients
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 6 months prior to screening

• Previous or concurrent malignancy with the following exceptions:

  • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
  • A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
• Investigational medicinal product within the last 30 days prior to screening
• Pregnant or nursing (lactating) women
• Intolerance to the excipients of the CTL019 cell product
• Cardiac arrhythmia not controlled with medical management
• Patients on oral anticoagulation therapy
• Prior treatment with any adoptive T cell therapy
• Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)

Other protocol-related inclusion/exclusion may apply.