Phase 2
Completed N=104
A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
Lymphoma, Non-Hodgkin · Lymphoma · Non-Hodgkin's Lymphoma · Lymphoma, Large B-Cell, Diffuse
Source: ClinicalTrials.gov NCT03744676 ↗
Enrolled (actual)
104
Serious AEs
58.5%
Results posted
Dec 2023
Primary outcomePrimary: Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3 — 0.0 Percentage of participants
Summary
This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3 |
0.0 | — |
| PRIMARY Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3 |
9.8 | — |
| PRIMARY Percentage of Participants With Infection Adverse Events Grade ≥ 3 |
11.0 | — |
| PRIMARY Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29. |
32.9 | — |
| SECONDARY Number of Participants With Adverse Events |
82 | — |
| SECONDARY Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology |
— | — |
| SECONDARY Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry |
— | — |
| SECONDARY Number of Participants With Adverse Events Grade ≥ 3 |
61 | — |
| SECONDARY Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS) |
0; 0 | — |
| SECONDARY Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT) |
9.5; 16.5 | — |
| SECONDARY Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS) |
7; 2; 7 | — |
| SECONDARY Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT) |
0; 12; 1 | — |
| SECONDARY Objective Response Rate (ORR) |
80.5 | — |
| SECONDARY Complete Response Rate (CRR) |
53.7 | — |
| SECONDARY Duration of Response (DoR) and Duration of Complete Response (DoCR) |
14.75; NA | — |
| SECONDARY Progression Free Survival (PFS) |
5.86 | — |
| SECONDARY Overall Survival (OS) |
21.88 | — |
| SECONDARY Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28) |
219760.3 | — |
| SECONDARY Maximum Observed Blood Concentration (Cmax) |
24077.8 | — |
| SECONDARY Time of Maximum Observed Blood Concentration (Tmax) |
10.0 | — |
| SECONDARY Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 |
-22.7; 1.5; -7.6; -3.0; 6.1; 2.7 | — |
| SECONDARY Mean Change From Baseline in EuroQol Instrument EQ-5D-5L. |
0.0 | — |
| SECONDARY Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization |
5.5; 15.0 | — |
| SECONDARY Number of Participants Who Received Transfusions |
43 | — |
| SECONDARY Number of Participants Requiring Growth Factor Support. |
35 | — |
| SECONDARY Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support |
12 | — |
Eligibility Criteria
Inclusion Criteria
- Age ≥ 18 years at the time of consent
- Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL from indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, primary mediastinal B-cell lymphoma(PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 systemic lines of therapy for DLBCL or after auto-HSCT.
- Positron-emission tomography-positive disease by Lugano Classification
- Eastern Cooperative Oncology Group performance status of 0 to 1
- Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function
- Adequate vascular access for leukapheresis procedure
- Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
- Subjects must agree to use appropriate contraception.
Exclusion Criteria
- Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
- History of prior allogeneic hematopoietic stem cell transplant
- Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
- History of another primary malignancy that has not been in remission for at least 2 years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on a Papanicolau smear.
- Active hepatitis B or hepatitis C infection at the time of screening
- History of or active human immunodeficiency virus infection at the time of screening
- Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or lisocabtagene maraleucel administration
- Presence of acute or chronic graft-versus-host disease
- History of clinically significant cardiac conditions within the past 6 months
- History or presence of clinically relevant CNS pathology such as epilepsy/seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
- Pregnant or nursing women
- Subject does not meet protocol-specified washout periods for certain prior treatments
- Prior CAR T-cell or other genetically modified T-cell therapy
- Progressive vascular tumor invasion, thrombosis, or embolism
- Venous thrombosis or embolism not managed on stable regimen of anticoagulation
- Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
Data sourced from ClinicalTrials.gov (NCT03744676). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.