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History of Changes for Study: NCT03484702
Trial to Determine the Efficacy and Safety of JCAR017 in Adult Subjects With Aggressive B-Cell Non-Hodgkin Lymphoma
Latest version (submitted June 23, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 26, 2018 None (earliest Version on record)
2 May 14, 2018 Study Status, Contacts/Locations and Study Identification
3 June 20, 2018 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 July 3, 2018 Study Status and Contacts/Locations
5 October 10, 2018 Contacts/Locations and Study Status
6 October 30, 2018 Contacts/Locations and Study Status
7 November 15, 2018 Study Status and Contacts/Locations
8 December 25, 2018 Study Status and Contacts/Locations
9 January 17, 2019 Contacts/Locations and Study Status
10 February 14, 2019 Outcome Measures, Study Status, Eligibility and Study Identification
11 February 22, 2019 Outcome Measures and Study Status
12 April 22, 2019 Study Status and Contacts/Locations
13 May 8, 2019 Study Status and Contacts/Locations
14 June 17, 2019 Study Status
15 August 20, 2019 Study Status and Contacts/Locations
16 October 20, 2019 Study Status and Contacts/Locations
17 December 2, 2019 Study Status, Contacts/Locations and Study Design
18 January 29, 2020 Study Status and Contacts/Locations
19 February 12, 2020 Outcome Measures, Study Status, Arms and Interventions, Study Description, Eligibility and Conditions
20 April 3, 2020 Study Status and Contacts/Locations
21 April 27, 2020 Contacts/Locations and Study Status
22 June 18, 2020 Study Status
23 December 3, 2020 Study Status and Contacts/Locations
24 June 14, 2021 Study Status, Contacts/Locations and Eligibility
25 January 21, 2022 Recruitment Status, Outcome Measures, Study Status, Contacts/Locations, Arms and Interventions, Study Design, Study Description, Eligibility and Study Identification
26 June 23, 2022 Study Status and Contacts/Locations
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Study NCT03484702
Submitted Date:  March 26, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: JCAR017-BCM-001
Brief Title: Trial to Determine the Efficacy and Safety of JCAR017 in Adult Subjects With Aggressive B-Cell Non-Hodgkin Lymphoma
Official Title: A Phase 2, Single-arm, Multi-cohort, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Adult Subjects With Aggressive B-Cell Non-Hodgkin Lymphoma
Secondary IDs: U1111-1209-4055 [Other Grant/Funding Number: WHO]
2017-000106-38 [EudraCT Number]
Open or close this module Study Status
Record Verification: March 2018
Overall Status: Not yet recruiting
Study Start: June 15, 2018
Primary Completion: June 15, 2022 [Anticipated]
Study Completion: June 15, 2022 [Anticipated]
First Submitted: March 26, 2018
First Submitted that
Met QC Criteria:
March 26, 2018
First Posted: April 2, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
March 26, 2018
Last Update Posted: April 2, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Celgene
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: Phase 2 single-arm, multi-cohort study to determine the efficacy and safety of JCAR017 (autologous T cells expressing anti-CD19 chimeric antigen receptor) in adult subjects with aggressive B-NHL (diffuse large B-cell lymphoma (DLBCL) NOS [de novo or transformed follicular lymphoma (tFL)], double/triple-hit lymphoma [DHL/THL], follicular lymphoma Grade 3B [FL3B], primary central nervous system lymphoma [PCNSL] and Richter's transformation).
Detailed Description:

This is a single-arm, multi-cohort, multi-center, Phase 2 study to determine the efficacy and safety of JCAR017 in adult subjects with aggressive B-cell NHL. The study will enroll subjects in Europe and Japan with DLBCL NOS (de novo or tFL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL), FL3B, PCNSL and Richter's transformation. Subjects with secondary central nervous system (CNS) involvement are allowed.

Once enrolled subjects will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, subjects will receive LD followed by infusion of JCAR017. JCAR017 will be administered at a dose of 1 x 10^8 JCAR017-positive transfected viable T cells by intravenous infusion.

Subjects 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.

Open or close this module Conditions
Conditions: Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkin lymphoma
Aggressive B-cell non-Hodgkin lymphoma
Diffuse large B-cell lymphoma
Relapse / refractory lymphoma
Transplant not eligible
Double-hit lymphoma
Triple-hit lymphoma
Primary/secondary central nervous system lymphoma
Richter's transformation/syndrome
Transformed follicular lymphoma
Follicular lymphoma Grade 3B
JCAR017
CAR T cell therapy
CD19 targeted therapy.
Efficacy and safety
Europe / Japan
TPTD
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 124 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Administration of JCAR017
JCAR017 will be infused at a dose of 1 x 10^8 JCAR017-positive transfected viable T cells (5×10^7 CD8+ CAR+ T cells and 5×10^7 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of lymphodepleting chemotherapy [LD]).
Drug: JCAR017
JCAR017
Open or close this module 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)
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)on the underlying chronic lymphocytic leukemia (CLL) in subjects with Richter´s transformation
[ Time Frame: Up to 2 years after JCAR017 infusion ]

Proportion of subjects achieving a CR, CR with incomplete bone marrow recovery (CRi), nodular PR (nPR), PR or PR with lymphocytosis (PRL) based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines
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 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. Pharmacokinetic - Cmax
[ Time Frame: Up to 2 years after JCAR017 infusion ]

Maximum concentration
9. Pharmacokinetic - Tmax
[ Time Frame: Up to 2 years after JCAR017 infusion ]

Time to peak concentration
10. Pharmacokinetic - 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 ]

European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire: The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of life.
12. Patient-Reported Outcomes - EQ-5D-5L
[ Time Frame: Up to 2 years after JCAR017 infusion ]

European Quality of Life-5 Dimensions health state classifier to 5 Levels questionnaire: EQ-5D is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal.
13. Patient-Reported Outcomes - FACT-Lym
[ 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.

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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 assessments/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, 1 or 2.
  6. Subjects with one of the following:
    • Cohort 1: Subjects with DLBCL NOS (de novo or tFL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B per WHO 2016 classification, 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), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B per WHO 2016 classification, 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. At the very least, subjects have to meet one of the following criteria: age ≥ 70 years, ECOG performance status ≥ 2, impaired pulmonary function DLCO ≤ 60%), impaired cardiac function (LVEF < 50%), impaired renal function (CrCl < 60 mL/min/1.73m2) or impaired hepatic function (AST/ALT > 2x ULN, bilirubin > 2 mg/dL or cirrhosis Child-Pugh B or C).
    • Cohort 3 (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2.
    • Cohort 4: Subjects with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) who failed first line therapy. Subjects may be screened at time of initial diagnosis and leukapheresis may be performed prior to initiation of first line therapy.
    • Cohort 5: Subjects with PCNSL after ≥ 1 line of therapy, including high-dose methotrexate.
    • Cohort 6: Subjects with Richter's transformation after ≥ 1 line of therapy for Richter's transformation.

    Note: Subjects with secondary DLBCL CNS involvement are eligible (not applicable for Cohort 5).

  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 subsequent therapies are given after last relapse with SD/PD as best response, the tissue from that last relapse will be considered adequate to participate in the trial.
  8. For subjects with NHL and Richter's transformed CLL: Subject must have positron emission tomography (PET)-positive disease as per Lugano Classification.
  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, 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 < 1.5 x age-adjusted upper limit of normal (ULN) or creatinine clearance > 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 < 3.0 mg/dL for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver).
    • Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and SaO2 ≥ 92% on room air.
    • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram or multigated acquisition (MUGA) scan performed within 4 weeks prior to leukapheresis.
  11. Adequate vascular access for leukapheresis procedure.
  12. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals until at least 12 months after the JCAR017 infusion and until CAR T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests, whichever occurs last.
  13. Female subjects of childbearing potential (FCBP) must:
    • Have two negative pregnancy tests as verified by the Investigator (one negative serum beta human chorionic gonadotropin [ß-hCG] pregnancy test result at screening and one negative serum pregnancy test within 48 hours prior to the first dose of LD chemotherapy). Subjects must agree to have another pregnancy test performed 90 days post JCAR017 infusion. This applies even if the subject practices true abstinence* from heterosexual contact.
    • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective and 1 additional effective (barrier) method of contraception from screening until at least 12 months following JCAR017 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests, whichever occurs last.
    • Agree to abstain from breastfeeding during study participation and for at least 90 days after JCAR017 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests, whichever occurs last.
  14. Male subjects must:
    • Practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study and until at least 12 months following JCAR017 infusion even if he has undergone a successful vasectomy and until CAR T cells are no longer present by qPCR on two consecutive tests, whichever occurs last.
      • True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Subject has any condition including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if participating in the study.
  3. Subject has any condition that confounds the ability to interpret data from the study.
  4. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV positive DLBCL of the elderly and Burkitt lymphoma.
  5. History of another primary malignancy that has not been in remission for at least 2 years prior to enrollment. The following are exempt from the 2-year limit if curatively treated:
    • Non-melanoma skin cancer
    • Localized prostate cancer
    • Cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear
  6. Treatment with any prior gene therapy product.
  7. Subjects who have received previous CD19-targeted therapy.
  8. Previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  9. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
  10. Presence of acute or chronic graft-versus-host disease (GVHD).
  11. Active autoimmune disease requiring immunosuppressive therapy.
  12. History of any one of the following cardiovascular conditions within the past 6 months:
    • Heart failure class III or IV as defined by the New York Heart Association (NYHA)
    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Other clinically significant cardiac disease
  13. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
  14. Pregnant or nursing women
  15. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
  16. Use of the following:
    • Therapeutic doses of corticosteroids (defined as > 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 (see below) 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, 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 antitumor 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.
    • Allogeneic HSCT within 90 days prior to leukapheresis.
  17. Prior hematopoietic stem cell transplant (only applicable to Cohort 2).
Open or close this module Contacts/Locations
Central Contact Person: Associate Director Clinical Trial Disclosure
Telephone: 1-888-260-1599
Email: clinicaltrialdisclosure@celgene.com
Study Officials: Claudia Schusterbauer, MD
Study Director
Celgene Corporation
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
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Available IPD/Information:

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