Ignite Creation Date:
2024-05-06 @ 8:05 PM
Last Modification Date:
2024-10-26 @ 3:20 PM
Study NCT ID:
NCT06247540
Status:
WITHDRAWN
Last Update Posted:
2024-02-29
First Post:
2023-12-08
Brief Title:
Venetoclax Rituximab and Nivolumab in Combination for the Treatment of Richters Transformation Arising From Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
Sponsor:
Northwestern University
Organization:
Northwestern University
Study Overview
Official Title:
Venetoclax Rituximab and Nivolumab Combination in Patients With Richters Transformation RT Arising From Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma CLLSLL A Phase II Study With Safety Run-In
Status:
WITHDRAWN
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial tests how well venetoclax rituximab and nivolumab works in treating patients with chronic lymphocytic leukemiasmall lymphocytic lymphoma CLLSLL with Richters transformation Richters transformation can be described as the development of an aggressive lymphoma in the setting of underlying CLLSLL that has a very poor prognosis with conventional therapies and represents a significant unmet medical need Venetoclax is in a class of medications called B-cell lymphoma-2 BCL-2 inhibitors It may stop the growth of cancer cells by blocking BCL-2 a protein needed for cancer cell survival Immunotherapy with monoclonal antibodies such as rituximab and nivolumab may help the bodys immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread Giving venetoclax rituximab and nivolumab together may work better than the conventional intensive immunochemotherapy to improve disease control in patients with Richters transformation arising from CLLSLL
Detailed Description:
PRIMARY OBJECTIVE
I To determine the preliminary efficacy in terms of overall response rate ORR per Lugano criteria with venetoclax nivolumab and rituximab combination in patients with Richters transformation
SECONDARY OBJECTIVES
I To determine the safety and tolerability of venetoclax nivolumab and rituximab combination in Richters transformation RT using Common Terminology Criteria for Adverse Events version 50 CTCAE v 50
II To determine preliminary efficacy in terms of complete response CR with venetoclax nivolumab and rituximab combination in patients with RT
III To determine the preliminary efficacy in terms of minimal residual disease MRD negativity rate with venetoclax nivolumab and rituximab combination in patients with RT
IV To determine the preliminary efficacy in terms of progression free survival PFS at 12 months with venetoclax nivolumab and rituximab combination in patients with RT
V To determine the preliminary efficacy in terms of overall survival OS with venetoclax nivolumab and rituximab combination in patients with RT
EXPLORATORY OBJECTIVES
I The study team will study various prognostic markers and biomarkers and correlate them with clinical response
Ia MRD status in bone marrow and peripheral blood Ib CLL prognostic markers cytogenetics abnormalities by fluorescence in situ hybridization FISH IgVH mutation status and TP53 mutation status Ic PD-L1 and PD-1 expression by immunohistochemistry IHC either in lymph node tissue samples or bone marrow Id T-cell subsets in the blood and tissue biopsy
EXPLORATORY STUDIES OBJECTIVES
I To determine the clinical and pathological factors impacting clinical response to the rituximab-nivolumab-venetoclax combination therapy
II To study the role of PD-1 blockade in RT III To determine the role of bone marrow and peripheral blood MRD in the RT study population
OUTLINE This is a dose-escalation study of venetoclax
Patients receive venetoclax orally PO once daily QD on days 1-28 nivolumab intravenously IV over 30 minutes on days 2 and 15 of cycles 1-4 and day 1 of each subsequent cycle and rituximab IV on day 2 of cycle 1 and day 1 of cycles 2-6 Treatment repeats every 28 days up to 6 cycles in the absence of disease progression or unacceptable toxicity After the completion of 6 cycles rituximab is discontinued and patients receive venetoclax PO QD on days 1-28 and nivolumab IV over 30 minutes on day 1 of each cycle Treatment repeats every 28 days for up to 2 years total therapy in the absence of disease progression or unacceptable toxicity Patients undergo tissue biopsy during screening Patients undergo a bone marrow biopsy and blood sample collection as well as positron emission tomography PETcomputed tomography CT and CT or magnetic resonance imaging MRI during screening and on the trial
After completion of study treatment patients are followed up at 30 days and every 90 days for 5 years from the start of treatment
I To determine the preliminary efficacy in terms of overall response rate ORR per Lugano criteria with venetoclax nivolumab and rituximab combination in patients with Richters transformation
SECONDARY OBJECTIVES
I To determine the safety and tolerability of venetoclax nivolumab and rituximab combination in Richters transformation RT using Common Terminology Criteria for Adverse Events version 50 CTCAE v 50
II To determine preliminary efficacy in terms of complete response CR with venetoclax nivolumab and rituximab combination in patients with RT
III To determine the preliminary efficacy in terms of minimal residual disease MRD negativity rate with venetoclax nivolumab and rituximab combination in patients with RT
IV To determine the preliminary efficacy in terms of progression free survival PFS at 12 months with venetoclax nivolumab and rituximab combination in patients with RT
V To determine the preliminary efficacy in terms of overall survival OS with venetoclax nivolumab and rituximab combination in patients with RT
EXPLORATORY OBJECTIVES
I The study team will study various prognostic markers and biomarkers and correlate them with clinical response
Ia MRD status in bone marrow and peripheral blood Ib CLL prognostic markers cytogenetics abnormalities by fluorescence in situ hybridization FISH IgVH mutation status and TP53 mutation status Ic PD-L1 and PD-1 expression by immunohistochemistry IHC either in lymph node tissue samples or bone marrow Id T-cell subsets in the blood and tissue biopsy
EXPLORATORY STUDIES OBJECTIVES
I To determine the clinical and pathological factors impacting clinical response to the rituximab-nivolumab-venetoclax combination therapy
II To study the role of PD-1 blockade in RT III To determine the role of bone marrow and peripheral blood MRD in the RT study population
OUTLINE This is a dose-escalation study of venetoclax
Patients receive venetoclax orally PO once daily QD on days 1-28 nivolumab intravenously IV over 30 minutes on days 2 and 15 of cycles 1-4 and day 1 of each subsequent cycle and rituximab IV on day 2 of cycle 1 and day 1 of cycles 2-6 Treatment repeats every 28 days up to 6 cycles in the absence of disease progression or unacceptable toxicity After the completion of 6 cycles rituximab is discontinued and patients receive venetoclax PO QD on days 1-28 and nivolumab IV over 30 minutes on day 1 of each cycle Treatment repeats every 28 days for up to 2 years total therapy in the absence of disease progression or unacceptable toxicity Patients undergo tissue biopsy during screening Patients undergo a bone marrow biopsy and blood sample collection as well as positron emission tomography PETcomputed tomography CT and CT or magnetic resonance imaging MRI during screening and on the trial
After completion of study treatment patients are followed up at 30 days and every 90 days for 5 years from the start of treatment
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-2023-08755 | REGISTRY | None | None |
| STU00219856 | None | None | None |
| NU 23H01 | OTHER | None | None |
| P30CA060553 | NIH | Northwestern University | httpsreporternihgovquickSearchP30CA060553 |