Clinical Trials Logo

Clinical Trial Summary

This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL. Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+ B-ALL) and Cohort 3 (r/r B-NHL, [DLBCL, BL, or PMBCL]). A Simon's Optimal two-stage study design will be applied to Cohort 1 and 2 in Phase 2.


Clinical Trial Description

This is a Phase 1/2, open-label, single arm, multicohort study incorporating Simon's Optimal two-stage design to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL. In the Phase 1, up to 5 dose levels will be of JCAR017 will be evaluated. Enrollment will commence in pediatric subjects with r/r B-ALL at Dose Level 1 (DL1) of 0.05x10^6 CAR+ T cells/kg (maximum DL1 of 5x10^6 JCAR017 CAR+ T cells [non-weight adjusted]). If this dose is confirmed to be safe and tolerable, additional subjects will be enrolled at higher dose(s) up to 0.75 x10^6 CAR+ T cells/kg (maximum of 75x10^6 JCAR017 CAR+ T cells [non-weight adjusted]) with the aim to identify the RP2D. Dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. A Safety Review Committee (SRC) will recommend the Phase 2 dose (defined as RP2D) based on an integrated assessment of the safety, PK and preliminary efficacy information from at least 10 pediatric subjects treated at the RP2D. In Phase 2, a minimum of 71 additional subjects (< 18 years of age) will be enrolled into one of the 3 cohorts listed below. The sample size for Cohorts 1 and 2 is calculated according to Simon's Optimal two-stage design. The 10 or more pediatric subjects treated at the RP2D in Phase 1 will form part of the sample size (ie, Cohort 1 and Cohort 2). Therefore, the protocol intends to treat 81 primary endpoint evaluable pediatric subjects in Phase 2, if warranted by the evaluation of results at the completion of the first stage of the study in each cohort. - Cohort 1 (r/r B-ALL): 48 evaluable pediatric subjects (13 subjects in Stage 1 and 35 in Stage 2) - Cohort 2 (MRD+ B-ALL): 23 evaluable pediatric subjects (9 subjects in Stage 1 and 14 subjects in Stage 2) - Cohort 3 (r/r B-NHL [DLBCL, BL, or PMBCL]): 10 evaluable pediatric subjects. Due to the very low incidence rate and therefore expected low subject accrual, there is no formal sample size for this arm. Up to 20 additional B-ALL subjects between 18 and 25 years of age may be enrolled in Phase 2. Following treatment with JCAR017 subjects will then enter the post-treatment period for disease progression/relapse, safety, CAR T cell persistence, and survival up to 24 months after administration of JCAR017. Efficacy will be assessed both locally and by an Independent Review Committee. Response assessments will be based on bone marrow and blood morphologic criteria, physical examination findings, along with laboratory assessments of cerebral spinal fluid (CSF) and bone marrow MRD (B-ALL only) assessments. B-NHL subjects will also have radiographic disease assessment by CT/MRI scans and tumor biopsies, if accessible. Post-study follow-up for survival, relapse, long-term toxicity, and lentiviral vector safety will continue under a separate long-term follow-up protocol for up to 15 years after the JCAR017 infusion as per health authority regulatory guidelines. An Independent Data Monitoring Committee will monitor the study conduct. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03743246
Study type Interventional
Source Celgene
Contact
Status Completed
Phase Phase 1/Phase 2
Start date October 17, 2018
Completion date January 26, 2024

See also
  Status Clinical Trial Phase
Recruiting NCT05540340 - A Study of Melphalan in People With Lymphoma Getting an Autologous Hematopoietic Cell Transplant Phase 1
Recruiting NCT04460235 - Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma Phase 4
Completed NCT03484702 - Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma Phase 2
Completed NCT01410630 - FLT-PET/CT vs FDG-PET/CT for Therapy Monitoring of Diffuse Large B-cell Lymphoma
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Completed NCT06190457 - Safety and Efficacy of Intrathecal Rituximab in 16 Children of Stage Ⅲ、ⅣNon-Hodgkin Lymphoma
Completed NCT02369016 - Phase III Copanlisib in Rituximab-refractory iNHL Phase 3
Recruiting NCT01676805 - Tissue Collection for Studies of Lymph Cancer
Terminated NCT00916045 - Pilot Study of Unrelated Cord Blood Transplantation Phase 2
Withdrawn NCT00538096 - A Phase I Study to Evaluate Safety, Tolerability in Adults With Lymphoma Phase 1
Terminated NCT00529503 - A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL Phase 2
Completed NCT00534989 - Use of FDG PET as Predictor of Residual Disease and Subsequent Relapse in Patients With NHL and HD Undergoing HDC and ASCT N/A
Completed NCT00156013 - Clofarabine for Relapsed or Refractory T-Cell or B-Cell Non-Hodgkin Lymphoma (NHL) Phase 1/Phase 2
Withdrawn NCT00319332 - A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen Phase 3
Completed NCT00322842 - Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients Phase 2
Completed NCT00141297 - A Study Of Oral Palbociclib (PD-0332991), A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer Phase 1
Completed NCT02509039 - A Study of CC-122 to Assess the Safety and Tolerability in Japanese Patients With Advanced Solid Tumors and Non-Hodgkin's Lymphoma (NHL) Phase 1
Completed NCT00268203 - Expanded Access Study Of BEXXAR® For Low Grade And Transformed Low-Grade Non-Hodgkin's Lymphoma Phase 2
Completed NCT01573000 - A Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL) Phase 2
Completed NCT03289182 - An Observational Study of MabThera Subcutaneous (SC) Safety in Participants With Non-Hodgkin's Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL)