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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02445248
Recruitment Status : Completed
First Posted : May 15, 2015
Last Update Posted : May 11, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This is a multi-center, phase II study to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory DLBCL.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma (DLBCL) Biological: Tisagenlecleucel Drug: Lymphodepleting chemotherapy Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Actual Study Start Date : July 29, 2015
Actual Primary Completion Date : December 22, 2022
Actual Study Completion Date : December 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tisagenlecleucel
Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who will receive tisagenlecleucel.
 Biological: Tisagenlecleucel
A single infusion of 5 x 10^8 viable CTL019 transduced cells, which will be administered via intravenous infusion.
Other Name: CTL019

Drug: Lymphodepleting chemotherapy
Prior to CTL019 cell infusion, an additional lymphodepleting chemotherapy cycle is planned. The use of any additional chemotherapy prior to the recommended lymphodepleting chemotherapy will be at the discretion of the investigator and dependent on the patient's disease burden. Lymphodepleting chemotherapy should be started 14 to 5 days before CTL019 infusion (D1) to allow for at least 48 hours from last dose of lymphodepleting chemotherapy to CTL019 infusion. The proposed lymphodepleting regimen is: Fludarabine (25 mg/m2 intravenously [i.v.] daily for 3 doses) and cyclophosphamide (250 mg/m2 i.v. daily for 3 doses starting with the first dose of fludarabine).


Outcome Measures
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Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Incidence and severity of adverse events (AEs) [ Time Frame: 5 years ]
  2. Time to response (TTR) [ Time Frame: 5 years ]
  3. Duration of overall response (DOR) [ Time Frame: 5 years ]
  4. Event free survival (EFS) [ Time Frame: 5 years ]
  5. Progression free survival (PFS) [ Time Frame: 5 years ]
  6. Overall survival (OS) [ Time Frame: 5 years ]
  7. In vivo cellular Pharmacokinetic (PK) profile of CTL019 transduced cells into target tissues [ Time Frame: 5 years ]
  8. Incidence of immunogenicity to CTL019 [ Time Frame: 5 years ]
  9. Number of Participants with presence of exposure to replication-competent lentivirus (RCL) as Assessed by quantitative polymerase chain reaction (qPCR) [ Time Frame: 5 years ]
  10. Prevalence of immunogenicity to CTL019 [ Time Frame: 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02445248


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02445248    
Other Study ID Numbers: CCTL019C2201
2014-003060-20 ( EudraCT Number )
First Posted: May 15, 2015    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Diffuse large B-cell lymphoma,
DLBCL,
Relapsed/refractory,
CTL019
 CART19
CART
CAR T cells
Chimeric antigen receptor
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Tisagenlecleucel
Antineoplastic Agents, Immunological
Antineoplastic Agents