Ignite Creation Date:
2024-05-06 @ 3:22 PM
Last Modification Date:
2024-10-26 @ 1:48 PM
Study NCT ID:
NCT04609046
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2020-10-29
Brief Title:
Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase I Trial of Methotrexate Rituximab Lenalidomide and Nivolumab Nivo-MR2 Induction Followed by Lenalidomide and Nivolumab Maintenance in Primary CNS Lymphoma
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Other - Awaiting amendment approval
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects best dose and effectiveness of lenalidomide when added to nivolumab and the usual drugs rituximab and methotrexate in patients with primary central nervous system CNS lymphoma Lenalidomide may stop or slow primary CNS lymphoma by blocking the growth of new blood vessels necessary for tumor growth Immunotherapy with monoclonal antibodies such as nivolumab may help the bodys immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread Methotrexate is frequently combined with other chemotherapy agents to improve response This study may help increase the understanding of lenalidomide and nivolumab use in primary CNS lymphoma treatment In addition it may help researchers see whether the control of CNS lymphoma can be extended by using these study drugs as maintenance prolonged therapy after control is achieved with the initial chemotherapy regimen induction
Detailed Description:
PRIMARY OBJECTIVES
I Determine the maximum tolerated dose MTD of lenalidomide when given in combination with high dose-methotrexate HD-MTX and rituximab with or without nivolumab as induction treatment of primary CNS lymphoma
II Determine the proportion of patients who are able to stay on maintenance therapy with lenalidomide andor nivolumab for 6 months after induction treatment of primary CNS lymphoma
SECONDARY OBJECTIVES
I To evaluate the overall response rate ORR of the combination of methotrexate rituximab lenalidomide nivolumab
II To evaluate the effect of the treatment regimen and lenalidomide nivolumab maintenance on progression free survival PFS
III To evaluate the effect of the treatment regimen and lenalidomide nivolumab maintenance on overall survival OS
EXPLORATORY OBJECTIVES
I To analyze tumor tissue and cerebrospinal fluid CSF for gene expression profiles and to correlate these profiles with treatment outcomes
II To determine whether CSF proteome and metabolome are predictors of outcomes prognostic marker
III To assess response to therapy and minimal residual disease via MRI-based metrics and minimal residual disease of blood and CSF
IV To evaluate the relationship between neurocognitive deficits and tumor and brain volumetrics as assessed by magnetic resonance imaging MRI and tumor metabolism
OUTLINE This is a dose-escalation study of lenalidomide
INDUCTION Patients receive rituximab intravenously IV on day 1 methotrexate IV over 2 hours or orally PO on day 2 lenalidomide PO daily on days 5-9 and nivolumab IV over 30 minutes on day 14 In dose level IV that includes nivolumab the doses of rituximab for cycles 2-6 may be given on the same day as nivolumab for the previous cycle Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity Patients who achieve complete response partial response or stable disease proceed to maintenance therapy
MAINTENANCE Within 6 weeks after the last dose of lenalidomide in induction therapy patients receive lenalidomide PO daily on days 1-21 and nivolumab IV over 30 minutes on day 1 Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity
Patients also undergo magnetic resonance imaging MRI throughout the trial computed tomography CT and positron emission tomography PETCT during screening and lumbar puncture at the end of the 6th cycle of induction and after 6 months of maintenance Patients may also undergo bone marrow aspirate and biopsy testicular ultrasound andor echocardiogram ECHO during screening
After completion of study treatment patients are followed up every 3 months for 2 years then every 6 months for up to 2 years
I Determine the maximum tolerated dose MTD of lenalidomide when given in combination with high dose-methotrexate HD-MTX and rituximab with or without nivolumab as induction treatment of primary CNS lymphoma
II Determine the proportion of patients who are able to stay on maintenance therapy with lenalidomide andor nivolumab for 6 months after induction treatment of primary CNS lymphoma
SECONDARY OBJECTIVES
I To evaluate the overall response rate ORR of the combination of methotrexate rituximab lenalidomide nivolumab
II To evaluate the effect of the treatment regimen and lenalidomide nivolumab maintenance on progression free survival PFS
III To evaluate the effect of the treatment regimen and lenalidomide nivolumab maintenance on overall survival OS
EXPLORATORY OBJECTIVES
I To analyze tumor tissue and cerebrospinal fluid CSF for gene expression profiles and to correlate these profiles with treatment outcomes
II To determine whether CSF proteome and metabolome are predictors of outcomes prognostic marker
III To assess response to therapy and minimal residual disease via MRI-based metrics and minimal residual disease of blood and CSF
IV To evaluate the relationship between neurocognitive deficits and tumor and brain volumetrics as assessed by magnetic resonance imaging MRI and tumor metabolism
OUTLINE This is a dose-escalation study of lenalidomide
INDUCTION Patients receive rituximab intravenously IV on day 1 methotrexate IV over 2 hours or orally PO on day 2 lenalidomide PO daily on days 5-9 and nivolumab IV over 30 minutes on day 14 In dose level IV that includes nivolumab the doses of rituximab for cycles 2-6 may be given on the same day as nivolumab for the previous cycle Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity Patients who achieve complete response partial response or stable disease proceed to maintenance therapy
MAINTENANCE Within 6 weeks after the last dose of lenalidomide in induction therapy patients receive lenalidomide PO daily on days 1-21 and nivolumab IV over 30 minutes on day 1 Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity
Patients also undergo magnetic resonance imaging MRI throughout the trial computed tomography CT and positron emission tomography PETCT during screening and lumbar puncture at the end of the 6th cycle of induction and after 6 months of maintenance Patients may also undergo bone marrow aspirate and biopsy testicular ultrasound andor echocardiogram ECHO during screening
After completion of study treatment patients are followed up every 3 months for 2 years then every 6 months for up to 2 years
Study Oversight
Has Oversight DMC:
None
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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2020-08331 | REGISTRY | None | None |
| A051901 | OTHER | None | None |
| A051901 | OTHER | None | None |
| U10CA180821 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180821 |