Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Active, not recruiting
First Posted : May 15, 2015
Last Update Posted : February 21, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 5, 2015
First Posted Date  ICMJE May 15, 2015
Last Update Posted Date February 21, 2019
Actual Study Start Date  ICMJE July 29, 2015
Estimated Primary Completion Date February 20, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2015)
Overall Response Rate (ORR) [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02445248 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2015)
  • Incidence and severity of adverse events (AEs) [ Time Frame: 5 years ]
  • Time to response (TTR) [ Time Frame: 5 years ]
  • Duration of overall response (DOR) [ Time Frame: 5 years ]
  • Event free survival (EFS) [ Time Frame: 5 years ]
  • Progression free survival (PFS) [ Time Frame: 5 years ]
  • Overall survival (OS) [ Time Frame: 5 years ]
  • In vivo cellular Pharmacokinetic (PK) profile of CTL019 transduced cells into target tissues [ Time Frame: 5 years ]
  • Incidence of immunogenicity to CTL019 [ Time Frame: 5 years ]
  • Number of Participants with presence of exposure to replication-competent lentivirus (RCL) as Assessed by quantitative polymerase chain reaction (qPCR) [ Time Frame: 5 years ]
  • Prevalence of immunogenicity to CTL019 [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2015)
  • Number of participants with adverse evensts (AEs) [ Time Frame: 5 years ]
  • Number of participants with serious adverse evensts (SAEs) [ Time Frame: 5 years ]
  • Time to response (TTR) [ Time Frame: 5 years ]
  • Duration of overall response (DOR) [ Time Frame: 5 years ]
  • Event free survival (EFS) [ Time Frame: 5 years ]
  • Progression free survival (PFS) [ Time Frame: 5 years ]
  • Overall survival (OS) [ Time Frame: 5 years ]
  • ORR, PFS, OS, EFS, DOR and AEs in histological and molecular subtypes [ Time Frame: 5 years ]
  • Characterize the in vivo cellular PK profile (levels, persistence, trafficking) of CTL019 transduced cells into target tissues (blood, bone marrow, cerebral spinal fluid (CSF) and other tissues if available) [ Time Frame: 5 years ]
  • Prevalence and Incidence of immunogenicity to CTL019 [ Time Frame: 5 years ]
  • RCL by VSV-g q-PCR [ Time Frame: 5 years ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-cell Lymphoma (DLBCL)
Intervention  ICMJE Biological: CTL019
Single arm
Study Arms Experimental: CTL019
Single arm
Intervention: Biological: CTL019
Publications * Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. doi: 10.1056/NEJMoa1804980. Epub 2018 Dec 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 20, 2019)
116
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2015)
100
Estimated Study Completion Date February 20, 2023
Estimated Primary Completion Date February 20, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   France,   Germany,   Italy,   Japan,   Netherlands,   Norway,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02445248
Other Study ID Numbers  ICMJE CCTL019C2201
2014-003060-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP