Aggressive B-cell Non Hodgkin Lymphoma (B-NHL) MedDRA version: 20.0 Level: LLT Classification code 10029593 Term: Non-Hodgkin's lymphoma NOS System Organ Class: 100000004864 MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disord
Conditions
Interventions
Product Name: JCAR017
Product Code: JCAR017
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous CD4+ and CD8+ T cells expressi
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 (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), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed first line therapy including an anthracycline and rituximab (or other CD-20-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 2x 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 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 (Cheson, 2014). 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, 2
Exclusion criteria
Exclusion criteria: 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 (see Section 8.2 for full details): • 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, cyclophosphamid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the efficacy, defined as overall response rate (ORR), of JCAR017 in subjects with aggressive B-cell non-Hodgkin lymphoma.; Secondary Objective: - To evaluate the safety and feasibility of administering JCAR017 - To evaluate ORR of JCAR017 in underlying chronic lymphocytic leukemia (CLL) in subjects with Richter’s transformation (Cohort 6) - To evaluate other measures of efficacy of JCAR017 ( e.g., complete response rate [CRR], event-free survival [EFS], progression-free survival [PFS], overall survival [OS], duration of response [DOR]) - Characterize the cellular pharmacokinetic (PK) profile of JCAR017, including the quantity and persistence of the chimeric antigen receptor (CAR) T cells in the peripheral blood - Describe changes in health-related quality of life using the European Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC QLQ-C30), the European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) "Additional concerns" scale ; Primary end point(s): - Non-Hodgkin lymphoma (NHL; including secondary central nervous system [CNS] involvement): Overall Response Rate (ORR) Cohorts 1, 2, 3, 4 and 6 - Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL): ORR Cohort 5 ;Timepoint(s) of evaluation of this end point: Up to 2 years after JCAR017 infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety - Underlying chronic lymphocytic leukemia (CLL) in subjects with Richter´s transformation: ORR Cohort 6 - Complete response rate (CRR) - Event-free survival (EFS) - Progression-free survival (PFS) - Overall survival (OS) - Duration of response (DOR) - PK - Patient-Reported Outcomes ;Timepoint(s) of evaluation of this end point: Up to 2 years after JCAR017 infusion | — |
Countries
Austria, Belgium, Finland, France, Germany, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed