JULIET: Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02445248

Collaborator

(none)

115

Enrollment

Locations

Arm

90.8

Anticipated Duration (Months)

4.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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: CTL019	Phase 2

Study Design

Study Type:

Interventional

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 :

Jul 29, 2015

Anticipated Primary Completion Date :

Feb 20, 2023

Anticipated Study Completion Date :

Feb 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CTL019 Single arm	Biological: CTL019 Single arm

Arm

Intervention/Treatment

Experimental: CTL019

Single arm

Biological: CTL019

Single arm

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [5 years]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic - Arizona Mayo Clinic Building	Phoenix	Arizona	United States	85054
2	University of California San Francisco SC-4	San Francisco	California	United States	94101
3	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia	United States	30322
4	University of Chicago Medical Center, Hematology & Oncology	Chicago	Illinois	United States	60637
5	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
6	The Sidney Kimmel Cancer Center at Johns Hopkins Hospital SC-2	Baltimore	Maryland	United States	21287-0013
7	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
8	University of Minnesota SC C2201	Minneapolis	Minnesota	United States	55455
9	Weill Cornell Medical College	New York	New York	United States	10021
10	Duke Unversity Medical Center	Durham	North Carolina	United States	27705
11	The Ohio State University James Cancer Hospital &	Columbus	Ohio	United States	43210
12	Oregon Health & Science University	Portland	Oregon	United States	97239
13	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	MD Anderson Cancer Center SC	Houston	Texas	United States	77030
15	Novartis Investigative Site	Camperdown		Australia	VIC 2050
16	Novartis Investigative Site	Melbourne		Australia	VIC 3002
17	Novartis Investigative Site	Vienna		Austria	A-1090
18	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
19	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
20	Novartis Investigative Site	Pierre Benite Cedex		France	69495
21	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
22	Novartis Investigative Site	Wuerzburg		Germany	97080
23	Novartis Investigative Site	Milano	MI	Italy	20133
24	Novartis Investigative Site	Fukuoka city	Fukuoka	Japan	812-8582
25	Novartis Investigative Site	Sapporo city	Hokkaido	Japan	060 8648
26	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104 0045
27	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
28	Novartis Investigative Site	Oslo		Norway	NO-0424