| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03575351 | A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas | PHASE3 | COMPLETED | 184 | — | — | Oct 23, 2018 | Oct 23, 2023 | Aug 3, 2025 | 54 | United States, Belgium +10 |
| NCT04245839 | A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL) | PHASE2 | ACTIVE NOT_RECRUITING | 276 | — | — | Jul 14, 2020 | Sep 30, 2031 | Nov 5, 2025 | 49 | United States, Austria +8 |
| NCT03484702 | Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma | PHASE2 | COMPLETED | 113 | — | — | Jun 5, 2018 | Dec 15, 2023 | Dec 27, 2024 | 20 | Austria, Belgium +9 |
| NCT03310619 | A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With Relapsed/Refractory B-cell Malignancies | PHASE1 | COMPLETED | 62 | — | — | Dec 20, 2017 | Feb 15, 2023 | Apr 4, 2024 | 9 | United States |
Time from randomization to death, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR) by 9 weeks or start of new antineoplastic therapy, whichever occurs first. CR: Target nodes masses must regress to ≤ 1.5cm in LDi, no extralymphatic sites, no new lesions. PR: ≥ 50% decrease in sum of diameters of up to 6 target nodes and extranodal sites, no new lesions, spleen must have regressed \> 50% in length. PD: LDi \> 1.5cm, increase by ≥ 50% from PPD nadir, an increase in LDi or SDi from nadir, 0.5 cm for lesions ≤ 2cm, 1.0cm for lesions \> 2cm. Complete metabolic response: Lymph nodes score 1, 2, 3 with/without residual mass on 5-point scale, no new lesions, no FDG-avid disease. Partial metabolic response: Lymph nodes score 4 or 5, reduced uptake from baseline, no new lesions, residual uptake higher than normal, reduced from baseline. Progressive metabolic disease: Score 4 or 5 with an increase in uptake intensity from baseline and/or new FDG-avid.
Is defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) at any time up to 60 months after JCAR017 treatment as assessed by PET-CT and/or CT using "The Lugano classification"
Overall response rate (ORR) by Independent Review Committee (Cohorts 1, 2, 3). ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: No * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: No * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: No * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall response rate (ORR) is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: None * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: None/normal * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall response rate (ORR) determined by Investigator assessment after JCAR017 infusion. The ORR is the percent of participants with best overall response (BOR) of either complete response (CR), complete response unconfirmed (Cru) or partial response (PR). Complete response (CR): * Brain imaging: No contrast enhancement * Corticosteroid dose: None * Eye examination: Normal * Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu): * Brain imaging: No contrast enhancement, Minimal abnormality * Corticosteroid dose: Any * Eye examination: Normal, minor RPE abnormality * Cerebrospinal fluid cytology: Negative Partial response (PR): * Brain imaging: 50% decrease in enhancing tumor, no contrast enhancement. * Corticosteroid dose: Irrelevant * Eye examination: Minor RPE abnormality, decrease in vitreous cells or retinal infiltrate. * Cerebrospinal fluid cytology: Negative, persistent or suspicious
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: * Results in death; * Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); * Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). * Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions); * Is a congenital anomaly/birth defect; * Constitutes an important medical event. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
Participants enrolled in Phase 1 are considered evaluable for DLTs if they received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and completed the specified DLT evaluation period or if they have received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and experience a DLT during the DLT evaluation period.
Percentage of participants achieving a complete response (CR). CR is complete radiologic response (CRR) and complete metabolic response (CMR). CR was measured using CT and PET and assessed for the presence of index and non-index lesions, spleen size, and the absence of new lesions or diseased bone marrow. To be considered as having CRR participants had to have all of the following: * Index lesions - longest transverse diameter of nodal lesions ≤ 1.5 cm and the absence of extranodal disease. * Non-index lesions - the absence of non-index lesions. * Spleen size \<13 cm * The absence of new lesions * Normal bone marrow assessment To be considered as having CMR participants had to have all of the following: * A score of 1, 2, or 3 with or without residual mass on 5-PS for index and non-index lesions. * The absence of new lesions * No evidence of FDG-avid disease in marrow and a normal bone marrow assessment
| Arm | Type | Description |
|---|---|---|
| Arm A - Standard of Care (SOC) | ACTIVE_COMPARATOR | Subjects should receive SOC (R-DHAP, R-ICE or R-GDP) followed by HDCT (BEAM) and HSCT. Standard of care regimen will be administered as per investigator decision. |
| Arm B - JCAR017 | EXPERIMENTAL | Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently followed by JCAR017 infusion. |
| Administration of JCAR017 | EXPERIMENTAL | * Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) and cyclophosphamide IV (300 mg/m2/day for 3 days) prior to JCAR017 infusion. Refer to the most recent package inserts for further details on administration of these agents. * JCAR017 will be infused on Day 1 at a target dose of 100 × 10\^6 CAR-positive viable T cells (CAR+ T cells), 2 to 7 days after completion of LD chemotherapy. Each JCAR017 dose includes CD4+ CAR+ T cells and CD8+ CAR+ T cells. |
| Arm A: JCAR017 in combination with Durvalumab | EXPERIMENTAL | JCAR017 will be administered at a single flat dose of 50 x 10\^6 CAR+T cells or 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules |
| Arm B: JCAR017 in combination with CC-122 | EXPERIMENTAL | This arm will test JCAR017 in combination with the CC-122. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses |
| Arm C: JCAR017 in combination with CC-220 | EXPERIMENTAL | This arm will test JCAR017 in combination with CC-220. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses |
| Arm D: JCAR017 in combination with Ibrutinib | EXPERIMENTAL | This arm will test JCAR017 in combination with ibrutinib. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at a fixed dose of 420 mg daily |
| Arm E: JCAR017 in combination with relatlimab and/or nivolumab | EXPERIMENTAL | This arm will test JCAR017 in combination with relatlimab and/or nivolumab in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules |
| Arm F: JCAR017 in combination with CC-99282 | EXPERIMENTAL | This arm will test JCAR017 in combination with CC-99282 in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules. |
| Name | Type | Description |
|---|---|---|
| Standard of Care | DRUG | Standard of Care |
| JCAR017 | GENETIC | JCAR017 |
| Fludarabine | DRUG | Fludarabine |
| Cyclophosphamide | DRUG | Cyclophosphamide |
| Durvalumab | DRUG | Anti-PD-L1 |
| CC-122 | DRUG | Pleiotropic Pathway Modifier |
| Ibrutinib | DRUG | Ibrutinib |
| CC-220 | DRUG | CC-220 |
| Relatlimab | DRUG | Relatlimab |
| Nivolumab | DRUG | Nivolumab |
| CC-99282 | DRUG | CC-99282 |
Inclusion Criteria: 1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF). 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), h...