Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients

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)

ClinicalTrials.gov Identifier: NCT02445248

Novartis Reference Number: CCTL019C2201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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 
Diffuse Large B-cell Lymphoma (DLBCL)
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
115 participants
Start date 
Jul 29, 2015
Completion date 
Feb 20, 2023
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Biological
CTL019
Single arm

Eligibility 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.

Study Locations

United States
Mayo Clinic - Arizona Mayo Clinic Building
-
Phoenix, 85054
Arizona
United States
University of California San Francisco SC-4
-
San Francisco, 94101
California
United States
Emory University School of Medicine/Winship Cancer Institute
-
Atlanta, 30322
Georgia
United States
University of Chicago Medical Center, Hematology & Oncology
-
Chicago, 60637
Illinois
United States
University of Kansas Cancer Center
-
Westwood, 66205
Kansas
United States
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital SC-2
-
Baltimore, 21287-0013
Maryland
United States
University of Michigan Health System
-
Ann Arbor, 48109
Michigan
United States
University of Minnesota SC C2201
-
Minneapolis, 55455
Minnesota
United States
Weill Cornell Medical College
-
New York, 10021
New York
United States
Duke Unversity Medical Center
-
Durham, 27705
North Carolina
United States
The Ohio State University James Cancer Hospital &
-
Columbus, 43210
Ohio
United States
Oregon Health & Science University
-
Portland, 97239
Oregon
United States
University of Pennsylvania
-
Philadelphia, 19104
Pennsylvania
United States
MD Anderson Cancer Center SC
-
Houston, 77030
Texas
United States
Australia
Novartis Investigative Site
-
Camperdown, VIC 2050
-
Australia
Novartis Investigative Site
-
Melbourne, VIC 3002
-
Australia
Austria
Novartis Investigative Site
-
Vienna, A-1090
-
Austria
Canada
Novartis Investigative Site
-
Hamilton, L8V 5C2
Ontario
Canada
Novartis Investigative Site
-
Montreal, H1T 2M4
Quebec
Canada
France
Novartis Investigative Site
-
Pierre Benite, 69310
-
France
Germany
Novartis Investigative Site
-
Koeln, 50937
Nordrhein-Westfalen
Germany
Novartis Investigative Site
-
Wuerzburg, 97080
-
Germany
Italy
Novartis Investigative Site
-
Milano, 20133
MI
Italy
Japan
Novartis Investigative Site
-
Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
-
Sapporo city, 060 8648
Hokkaido
Japan
Novartis Investigative Site
-
Chuo ku, 104 0045
Tokyo
Japan
Netherlands
Novartis Investigative Site
-
Amsterdam, 1105 AZ
-
Netherlands
Norway
Novartis Investigative Site
-
Oslo, NO-0424
-
Norway

Have a question?

Call 1-999-669-6682 or email [email protected]