Clinical Trials Logo

Clinical Trial 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.


Clinical Trial 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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03558750
Study type Interventional
Source Vanderbilt-Ingram Cancer Center
Contact
Status Terminated
Phase Phase 1
Start date June 14, 2018
Completion date April 16, 2019

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04572763 - Copanlisib Plus Venetoclax in R/R DLBCL Phase 1/Phase 2
Recruiting NCT06047197 - Phase I Clinical Trial of RC19D2 Cell Injection in the Treatment of Diffuse Large B-cell Lymphoma Phase 1
Active, not recruiting NCT03136497 - A Study of ABT-199 Plus Ibrutinib and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma Phase 1
Completed NCT03287817 - CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma Phase 1/Phase 2
Recruiting NCT05890352 - Study Adding Drugs to Usual Treatment for Large B-Cell Lymphoma That Returned or Did Not Respond to Treatment Phase 2
Active, not recruiting NCT03321643 - Testing the Addition of an Immunotherapy Agent, Atezolizumab, When Given With the Usual Chemo-Immunotherapy Drug Combination (Rituximab Plus Gemcitabine and Oxaliplatin) for Relapsed/Refractory (That Has Come Back or Not Responded to Treatment) Transformed Diffuse Large B-Cell Lymphoma Phase 1
Recruiting NCT05052528 - Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma Phase 1
Recruiting NCT04384484 - Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Phase 3
Active, not recruiting NCT03259503 - Olaparib and High-Dose Chemotherapy in Treating Patients With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplant Phase 1
Active, not recruiting NCT01955499 - Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma Phase 1
Completed NCT02219737 - Ibrutinib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma Phase 1
Active, not recruiting NCT03583424 - Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan Before Stem Cell Transplant in Treating Participants With Relapsed or Refractory Non-Hodgkin Lymphoma Phase 1/Phase 2
Completed NCT02874404 - TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Phase 2
Recruiting NCT04007029 - Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia Phase 1
Withdrawn NCT03579927 - CAR.CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood NK Cells, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Participants With B-cell Lymphoma Phase 1/Phase 2
Terminated NCT03272633 - Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies Early Phase 1
Completed NCT03309878 - Mogamulizumab and Pembrolizumab in Treating Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma Phase 1/Phase 2
Completed NCT02405078 - Tumor-Specific Clonotype, Metabolic Profile, and PET/CT in Predicting Chemotherapy Response in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma Early Phase 1
Completed NCT03019640 - Umbilical Cord Blood NK Cells, Rituximab, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma Phase 2
Active, not recruiting NCT03892044 - Duvelisib and Nivolumab in Treating Patients With Richter Syndrome or Transformed Follicular Lymphoma Phase 1