Ignite Creation Date:
2025-12-24 @ 5:00 PM
Ignite Modification Date:
2026-01-04 @ 4:56 PM
Study NCT ID:
NCT03558750
Status:
TERMINATED
Last Update Posted:
2019-04-25
First Post:
2018-06-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Rituximab, Lenalidomide, and Nivolumab in Treating Participants With Relapsed or Refractory Non-Germinal Center Type Diffuse Large B Cell Lymphoma or Primary Central Nervous System Lymphoma
Sponsor:
Vanderbilt-Ingram Cancer Center
Organization:
Study Overview
Official Title:
Combination of Rituximab, Lenalidomide and Nivolumab for Relapsed/ Refractory Non-germinal Center (Non-GCB) Type Diffuse Large B Cell Lymphoma (DLBCL) Including Primary Central Nervous System Lymphoma (PCNSL): A Phase 1/2 Trial
Status:
TERMINATED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the side effects and best dose of lenalidomide when given in combination with rituximab and nivolumab and how well they work in treating participants with non-germinal center type diffuse large B cell lymphoma or primary central nervous system lymphoma that has come back or isn't responding to treatment. Monoclonal antibodies, such as rituximab and nivolumab, may interfere with ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab, lenalidomide, and nivolumab may work better in treating participants with diffuse large B cell lymphoma.
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and toxicity profile of lenalidomide in combination with standard doses of rituximab and nivolumab in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) (non-germinal center B cell \[non-GCB\]) and in primary central nervous system (CNS) lymphoma (PCNSL) (Phase I).
II. Evaluate the efficacy of lenalidomide in combination with standard doses of rituximab and nivolumab in R/R non-GCB type DLBCL and PCNSL (Phase II).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of nivolumab when combined with lenalidomide and rituximab.
II. To determine the time to progression (complete response, partial response or stable disease), progression free survival (PFS) and overall survival (OS).
III. To evaluate the difference in overall response rate between those with and without programmed cell death ligand 1 (PD-L1) protein expression in tumor (subgroup analysis).
IV. To evaluate the difference in overall response rate between those with and without MYD88 mutation in tumor (subgroup analysis).
EXPLORATORY OBJECTIVES:
I. To perform PD-L1, PD-1 expression on tumor cells by immunohistochemistry including double staining for PAX-5 and PD-L1 and CD68 and PD-L1, CD3/CD4/CD8 for T cell infiltration, CD68 for tumor associated macrophages.
II. To assess for presence of MYD88 L265 mutation by allele specific polymerase chain reaction (PCR) in tumor tissue and /or cerebrospinal fluid (CSF) (where lumbar puncture is clinically performed).
III. To perform fluorescence in situ hybridization (FISH) for 9p24.1/ PD-L1/PD-L2 locus.
IV. To evaluate MYD88 PCR on CSF (where available). V. To perform gene expression panel for tumor immune response in tumor samples (prioritizing cases in which a second serial biopsy is available).
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
Participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15, rituximab IV on day 1, and lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to of 8 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or stable disease at the end of 8 cycles will be offered lenalidomide and nivolumab maintenance for up to 12 courses.
After completion of study treatment, participants are followed up every 3 months for 2 years and then every 6 months until year 4.
I. Determine the maximum tolerated dose and toxicity profile of lenalidomide in combination with standard doses of rituximab and nivolumab in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) (non-germinal center B cell \[non-GCB\]) and in primary central nervous system (CNS) lymphoma (PCNSL) (Phase I).
II. Evaluate the efficacy of lenalidomide in combination with standard doses of rituximab and nivolumab in R/R non-GCB type DLBCL and PCNSL (Phase II).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of nivolumab when combined with lenalidomide and rituximab.
II. To determine the time to progression (complete response, partial response or stable disease), progression free survival (PFS) and overall survival (OS).
III. To evaluate the difference in overall response rate between those with and without programmed cell death ligand 1 (PD-L1) protein expression in tumor (subgroup analysis).
IV. To evaluate the difference in overall response rate between those with and without MYD88 mutation in tumor (subgroup analysis).
EXPLORATORY OBJECTIVES:
I. To perform PD-L1, PD-1 expression on tumor cells by immunohistochemistry including double staining for PAX-5 and PD-L1 and CD68 and PD-L1, CD3/CD4/CD8 for T cell infiltration, CD68 for tumor associated macrophages.
II. To assess for presence of MYD88 L265 mutation by allele specific polymerase chain reaction (PCR) in tumor tissue and /or cerebrospinal fluid (CSF) (where lumbar puncture is clinically performed).
III. To perform fluorescence in situ hybridization (FISH) for 9p24.1/ PD-L1/PD-L2 locus.
IV. To evaluate MYD88 PCR on CSF (where available). V. To perform gene expression panel for tumor immune response in tumor samples (prioritizing cases in which a second serial biopsy is available).
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
Participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15, rituximab IV on day 1, and lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to of 8 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or stable disease at the end of 8 cycles will be offered lenalidomide and nivolumab maintenance for up to 12 courses.
After completion of study treatment, participants are followed up every 3 months for 2 years and then every 6 months until year 4.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2018-01092 | REGISTRY | NCI, Clinical Trials Reporting Program | View |