About Bolder Science

Our mission is to provide healthcare professionals with unbiased clinical research information, easily.

Currently, you can access the following clinical trials being conducted worldwide:

354,475 studies
in
216 countries
Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 12/03/2020.
This website is for US healthcare professionals

Log In to Bolder Science

or

Don't have an account? Sign Up

Please enter your email address.

You will receive a link to create a new password via email.

Log In

Create an Account

or
(optional) ?

Welcome, !

Please complete the following 4 questions to ensure you receive the information that best suits your needs.

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

finding clinical trials in which to enroll my patients

Rarely Often

finding newly launched clinical trials (for all phases)

Rarely Often

updates on status changes for clinical trials

Rarely Often

pipeline molecules

Rarely Often

Drug Interventions

Enter up to 3 drug interventions you are currently interested in:

Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 12/03/2020.

Trial to Determine the Efficacy and Safety of JCAR017 in Adult Subjects With Aggressive B-Cell Non-Hodgkin Lymphoma

Clinicaltrials.gov identifier NCT03484702

Recruitment Status Recruiting

First Posted April 2, 2018

Last update posted June 22, 2020

Study Description

Brief summary:

This open-label Phase 2 study will evaluate the safety and efficacy of modified T cells (JCAR017) administered to adult patients with aggressive B-cell non-Hodgkin lymphoma (NHL). The study will also help determine how long the modified T cells stay in the patient's body. Furthermore, changes in the patient's quality of life will be described. Phase 2 (autologous T cells expressing anti-CD19 chimeric antigen receptor) (DLBCL NOS [de novo or tFL], follicular lymphoma Grade 3B [FL3B], high grade B-cell Lymphoma [HGBL] and primary central nervous system lymphoma [PCNSL]).

  • Condition or Disease:Lymphoma, Non-Hodgkin
  • Intervention/Treatment: Drug: JCAR017
  • Phase: Phase 2
Detailed Description

This is a single-arm, multi-cohort, multi-center, Phase 2 study to determine the efficacy and safety of JCAR017 in adult patients with aggressive B-cell NHL. The study will enroll patients in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Patients with secondary central nervous system (CNS) involvement are allowed. Once enrolled, patients will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, patients will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells by intravenous infusion. Patients will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life. Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 116 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 2, Single-arm, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or With Other Aggressive B-Cell Malignancies
  • Actual Study Start Date: June 2018
  • Estimated Primary Completion Date: August 2021
  • Estimated Study Completion Date: June 2023
Arms and interventions
Arm Intervention/treatment
Experimental: Administration of JCAR017
JCAR017 will be infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of lymphodepleting chemotherapy (LD) chemotherapy)
Drug: JCAR017
JCAR017
Outcome Measures
  • Primary Outcome Measures: 1. Overall Response Rate (ORR) of JCAR017 in subjects with Non-Hodgkin Lymphoma (NHL; including secondary central nervous system (CNS) involvement) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Proportion of subjects achieving a complete response (CR) or partial response (PR) based on the Lugano classification (Cheson, 2014)
  • 2. ORR of JCAR017 in subjects with relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Proportion of subjects achieving a CR/complete response unconfirmed (CRu) or PR based on the International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma (Abrey, 2005)
  • 3. Adverse Events (AEs) in subjects intended to be treated as outpatients [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Type, frequency, and severity of all AEs, including serious adverse events (SAEs) and laboratory abnormalities
  • Secondary Outcome Measures: 1. Adverse Events (AEs) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Type, frequency, and severity of AEs, including serious adverse events (SAEs) and laboratory abnormalities
  • 2. Overall Response Rate (ORR) in subjects intended to be treated as outpatients [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Proportion of subjects achieving a complete response (CR) or partial response (PR) based on the Lugano classification (Cheson, 2014)
  • 3. Complete response rate (CRR) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Proportion of subjects achieving a CR (or CR and CRu for subjects with PCNSL) following JCAR017 infusion
  • 4. Event-free survival (EFS) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Time from JCAR017 infusion to death from any cause, progressive disease (PD), or starting a new anticancer therapy, whichever occurs first
  • 5. Progression-free survival (PFS) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Time from JCAR017 infusion to the first documentation of PD, or death due to any cause, whichever occurs first
  • 6. Overall survival (OS) [ Time Frame: Up to 2 years after last patient's JCAR017 infusion ]
    Time from JCAR017 infusion to time of death due to any cause
  • 7. Duration of response (DOR) [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Time from first response to progressive disease or death from any cause, whichever occurs first
  • 8. Pharmacokinetics by quantitative polymerase chain reaction (qPCR) - Cmax [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Maximum concentration
  • 9. Pharmacokinetics by qPCR - Tmax [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Time to peak concentration
  • 10. Pharmacokinetics by qPCR - AUC [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Area under the curve
  • 11. Patient-Reported Outcomes - EORTC QLQ-C30 [ Time Frame: Up to 2 years after JCAR017 infusion ]
    The European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire will be used as a measure of health-related quality of life
  • 12. Patient-Reported Outcomes - FACT-LymS [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale: Only the LYM subscale will be administered in this study. This scale addresses symptoms and functional limitations (15 item) that are important to lymphoma patients.
  • 13. Adverse Events (AEs) in subjects treated as outpatients [ Time Frame: Up to 2 years after JCAR017 infusion ]
    Type, frequency, and severity of AEs, including serious adverse events (SAEs) and laboratory abnormalities
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)

2. Subject must understand and voluntarily sign an ICF prior to any study-related
ssessments/procedures being conducted

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements

4. Investigator considers the subject is appropriate for adoptive T cell therapy

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects not
eligible for transplant (TNE) in Cohorts 2 and 3 and subjects in Cohort 5 may be
enrolled with ECOG of 2 only if they meet all other inclusion/exclusion criteria.

6. Subjects with one of the following:

Cohort 1: Subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016
classification (Swerdlow, 2016), after ≥ 2 lines of therapy*, including an
anthracycline and rituximab (or other CD20-targeted agent) Cohort 2: Transplant not
eligible subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016
classification (Swerdlow, 2016), who failed first line therapy*, including an
anthracycline and rituximab (or other CD20-targeted agent)

- Transplant not eligible subjects will include those who are deemed ineligible for
high-dose chemotherapy and HSCT due to age, performance status or comorbidity,
while also having adequate organ function for CAR T cell treatment. At the very
least, subjects have to meet one of the following criteria:

1. Age ≥ 70 years

2. ECOG performance status ≥ 2

3. Impaired pulmonary function (DLCO ≤ 60%, adjusted for hemoglobin
concentration using the Dinakara equation)

4. Impaired cardiac function (LVEF < 50%) 5. Impaired renal function (CrCl 2 x ULN, bilirubin ≥ 2 mg/dL or
cirrhosis Child-Pugh B or C)

- Subjects must fulfil all other in- and exclusion criteria Cohort 3 (Japan only):
Subjects meeting eligibility criteria for either Cohort 1 or 2 Cohort 4: Subjects
with newly diagnosed HGBL. Subjects must be eligible for anthracycline and
rituximab (or other CD20-targeted agent) containing regimen as induction prior to
consolidation with JCAR017** Cohort 5: Subjects with PCNSL who failed first line
therapy with HDCT and ASCT Cohort 6: (REMOVED) Cohort 7: Subjects meeting
eligibility criteria for Cohort 1 and suitable for outpatient treatment***

- For subjects with transformed disease, the subject should have had at least
2 lines of systemic therapy for his/her transformed disease (ie, DLBCL) for
Cohort 1 and 1 line for Cohort 2 to be eligible. Lines of therapy do not
include those given for a previously indolent condition (ie, follicular
lymphoma). Subjects do NOT have to have anthracycline for their DLBCL if
received for indolent disease.

- For subjects already undergoing anthracycline and rituximab containing
regimen, eligibility is to be discussed with Medical Monitor. Subjects
with complete metabolic response after 2 cycles of induction will
proceed with JCAR017 infusion only at time of relapse, if applicable.

- Subjects must meet the conditions for outpatient treatment and
monitoring as outlined in the Outpatient Administration and
Monitoring Guidance for Lisocabtagene Maraleucel.

Note: Subjects with secondary CNS lymphoma involvement may enroll in Cohorts 1 to 4
and 7; subjects with PCNSL are eligible for Cohort 5. Subject selection must consider
clinical risk factors for severe adverse events (AEs) and alternative treatment
options. Subjects should only be enrolled if the Investigator considers the potential
benefit outweighs the risk for the subject. For Cohort 5 and to not compromise safety,
subject selection has been restricted to those fit enough to HDCT and ASCT as their
prior therapy.

7. Histological confirmation of diagnosis at last relapse. Enough tumor material must be
available for central confirmation of diagnosis, otherwise a new tumor biopsy is
mandated.

Note: If the subject did not experience CR since last biopsy, the most recent biopsy
will be considered adequate to participate in the trial. For subjects with PCNSL, at a
minimum, corresponding pathology report is required if archival tumor material is not
available and repeated biopsy not feasible.

8. (REMOVED) For subjects with NHL and Richter's transformed CLL

9. For subjects with PCNSL: Subjects must have disease that is objectively measurable by
International Workshop to Standardize Baseline Evaluation and Response Criteria in
Primary Central Nervous System (CNS) Lymphoma (Abrey, 2005), cerebrospinal fluid (CSF)
cytology (in case of leptomeningeal only disease), or vitreal aspiration cytology
and/or retinal photographs (in case of ocular lymphoma if clinically indicated)

10. Adequate organ function, defined as:

- Adequate bone marrow function to receive LD chemotherapy as assessed by the
Investigator

- Serum creatinine 30 mL/min (estimated
glomerular filtration rate [eGFR] by Cockroft Gault)

- Alanine aminotransferase (ALT) ≤ 5 x ULN and total bilirubin < 2.0 mg/dL (or 20 mg/day prednisone or
equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017
infusion. Physiologic replacement, topical, and inhaled steroids are permitted.

- Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2)
given after leukapheresis to maintain disease control must be stopped ≥ 7 days
prior to LD chemotherapy

- Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1
week prior to leukapheresis. Oral anticancer agents, including lenalidomide and
ibrutinib, are allowed if at least 3 half-lives have elapsed prior to
leukapheresis

- Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide > 300 mg/m2,
ifosfamide, bendamustine) within 2 weeks prior to leukapheresis

- Experimental agents within 4 weeks prior to leukapheresis unless no response or
progressive disease (PD) is documented on the experimental therapy and at least 3
half-lives have elapsed prior to leukapheresis

- Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017
infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics,
mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as
anti-tumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R)

- Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion

- Radiation within 6 weeks prior to leukapheresis. Subjects must have progressive
disease in irradiated lesions or have additional non-irradiated, PET-positive
lesions to be eligible. Radiation to a single lesion, if additional
non-irradiated, measurable PET-positive lesions are present, is allowed up to 2
weeks prior to leukapheresis. Prior WBRT for subjects enrolled in Cohort 5 is not
allowed

- Allogeneic HSCT within 90 days prior to leukapheresis

- Prior hematopoietic stem cell transplant (only applicable to Cohort 2) Systemic
immunostimulatory agents (including but not limited to interferon and IL-2)
within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to
JCAR017 infusion

17. Progressive vascular tumor invasion, thrombosis, or embolism

18. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation

19. Known severe hypersensitivity to DMSO or Dextran

Contacts and Locations
Contacts

Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
Show 20 Study Locations
Sponsors and Collaborators

Celgene

Investigators

Study Director: Claudia Schusterbauer, MD Celgene Corporation

More Information
  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT03484702 History of Changes
  • Other Study ID Numbers: JCAR017-BCM-001, U1111-1209-4055, 2017-000106-38
  • First Posted: April 2, 2018 Key Record Dates
  • Last Update Posted: June 22, 2020
  • Last Verified: June 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Keywords provided by Celgene: Non-Hodgkin lymphoma
    Aggressive B-cell non-Hodgkin lymphoma
    Diffuse large B-cell lymphoma
    Relapse / refractory lymphoma
    Transplant not eligible
    High-grade B-cell lymphoma
    Primary central nervous system lymphoma
    Transformed follicular lymphoma
    Follicular lymphoma Grade 3B
    JCAR017
    Liso-Cel
  • Additional relevant MeSH terms: Lymphoma
    Lymphoma, Non-Hodgkin
    Aggression