Lymphoma
Conditions
Keywords
primary CNS lymphoma, newly diagnosed, JCAR017
Brief summary
The purpose of this study is to evaluate the safety and efficacy of lisocabtagene maraleucel (Breyanzi/liso-cel/BMS-986387) in adults as first-line treatment in transplant-ineligible Primary Central Nervous System Lymphoma (PCNSL).
Interventions
DRUGRituximab
Specified dose on specified days
DRUGMethotrexate
Specified dose on specified days
DRUGProcarbazine
Specified dose on specified days
DRUGTemozolomide
Specified dose on specified days
BIOLOGICALLiso-cel
Specified dose on specified days
DRUGFludarabine
Specified dose on specified days
DRUGCyclophosphamide
Specified dose on specified days
DRUGCalcium folinate
Specified dose on specified days
Sponsors
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 years or older at the time of signing the informed consent form (ICF). * Histologically confirmed primary central nervous system (CNS) lymphoma (PCNSL) prior to screening, as assessed by local pathology. * Transplant-ineligible based on physician's assessment and meeting at least one of the following criteria: age ≥65 years or HCT-CI (Hematopoietic Cell Transplantation-specific Comorbidity Index) score ≥3. * Participant must be suitable, per investigator, to receive a high dose methotrexate (HD-MTX) based treatment regimen. * Prior to signing ICF, anti-cancer therapy for the treatment of PCNSL must be limited to HD-MTX based standard of care regimens with a minimum of 4 and maximum of 6 doses of MTX. Corticosteroids used as part of standard-of-care management for PCNSL symptom control are permitted prior to ICF signature but must be discontinued at the time of ICF signature. For medical conditions other than PCNSL, non-therapeutic corticosteroids use may be permitted on study. * Prior to enrollment, participant's disease must be sensitive to prior high-dose methotrexate-based (HD-MTX) regimens, as demonstrated by a complete response (CR, no remaining signs of PCNSL) or a partial response (PR, signs of PNCSL mostly gone) per Investigator's assessment, based on the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * No prior experimental treatments for PCNSL. * Individuals of childbearing potential (IOCBP) must have a negative highly sensitive pregnancy test within 24 hours prior to the start of study intervention.
Exclusion criteria
* Participant has a diagnosis of secondary CNS lymphoma due to systemic disease. * Primary intraocular lymphoma (PIOL)/ Primary vitreoretinal lymphoma (PVRL), isolated cerebrospinal fluid (CSF) disease, or a relapsed or refractory PCNSL. * Any significant medical condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she was to participate in the study based on investigator's judgement. * History of another primary malignancy that has not been in remission for ≥2 years. a. Exceptions include certain adequately treated non-invasive malignancies, localized prostate cancer treated with curative intent, and completely resected Stage 1 solid tumors with a low risk of recurrence. * Prior treatment with CAR T-cell or any other gene therapy product that utilizes human genome-editing technology. * History of or active human immunodeficiency virus (HIV). * Active hepatitis B or active hepatitis C. * Active autoimmune disease requiring immunosuppressive therapy. * History of prior allogeneic transplant, or solid organ transplant requiring immunosuppressive therapy. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 12 months after liso-cel infusion | Defined as the time from the date of liso-cel infusion to the date of first documented disease relapse or progression as assessed by the investigator, or death from any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 12 months after date of enrollment | Defined as the time from the date of enrollment to the date of first documented disease relapse or progression as assessed by the investigator, or death from any cause, whichever occurs first |
| Modified Progression-free Survival (mPFS) | 12 months after date of enrollment | Defined as the time from the date of enrollment to the date of first documented disease relapse or progression as assessed by the investigator, or death from any cause, whichever occurs first. Disease relapse or progression prior to liso-cel infusion is considered as an event only if the patient does not achieve complete response (CR) after liso-cel infusion. |
| Complete Response Rate (CRR) | Up to end of study (approximately 2 years) | Defined as proportion of patients achieving CR at any time between liso-cel infusion and the date of first documented disease relapse or progression as assessed by the investigator, initiation of a new antineoplastic therapy to treat Primary Central Nervous System Lymphoma (PCNSL), or end of study, whichever occurs first |
| Overall Response Rate (ORR) | Up to end of study (approximately 2 years) | Defined as proportion of patients achieving CR or Partial Response (PR) at any time between liso-cel infusion and the date of first documented disease relapse or progression as assessed by the investigator, initiation of a new antineoplastic therapy to treat PCNSL, or end of study, whichever occurs first |
| Duration of Response (DoR) | 12 months after liso-cel infusion | Defined as the time from the date of first documented disease response (complete response \[CR\] or partial response \[PR\]) achieved after liso-cel infusion to the date of first subsequent documented disease relapse or progression as assessed by the investigator, or death from any cause |
| Event-free Survival (EFS) | 12 months after date of enrollment | Defined as the time from the date of enrollment to the date of first documented disease relapse or progression as assessed by the investigator, or initiation of new antineoplastic therapy to treat PCNSL, or death from any cause, whichever occurs first |
| Overall Survival (OS) | 12 months after date of enrollment | Defined as the time from the date of enrollment to the date of death from any cause |
| Number of participants with adverse events (AEs) | Up to end of study (approximately 2 years) | — |
| Number of participants with serious adverse events (SAEs) | Up to end of study (approximately 2 years) | — |
| Number of participants with adverse events of special interest (AESIs) | Up to end of study (approximately 2 years) | — |
| Number of participants with laboratory abnormalities | Up to end of study (approximately 2 years) | — |
| Health-related quality of life (HRQoL) | Up to end of study (approximately 2 years) | As assessed by the European Organisation for Research and Treatment of Cancer--Quality of Life C30 Questionnaire (EORTC-QLQ-30) |
| Neurocognitive performance (Trial Making Test - Parts A and B) | Up to end of study (approximately 2 years) | Change from baseline over time in neurocognitive functions assessed using the Trail Making Test (TMT) |
| Neurocognitive performance (Montreal Cognitive Assessment (MoCA)) | Up to end of study (approximately 2 years) | Change from baseline over time in neurocognitive functions assessed using the Montreal Cognitive Assessment (MoCA) |
Countries
France, Germany, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed