Ignite Creation Date:
2025-12-25 @ 3:39 AM
Ignite Modification Date:
2025-12-26 @ 2:23 AM
Study NCT ID:
NCT04840602
Status:
SUSPENDED
Last Update Posted:
2025-12-24
First Post:
2021-04-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib and Rituximab) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Randomized Study Comparing Ibrutinib and Rituximab vs. Venetoclax and Rituximab in Previously Untreated Waldenström's Macroglobulinemia (WM) / Lymphoplasmacytic Lymphoma (LPL)
Status:
SUSPENDED
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Other - For RRA for Venetoclax issued 10/17/2025
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab in treating patients with previously untreated Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. 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. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib and rituximab alone.
Detailed Description:
PRIMARY OBJECTIVE:
I. To compare the rate of very good partial response or better (VGPR or better) in previously untreated participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib plus rituximab (IR) versus (vs.) venetoclax plus rituximab (VR) regimen.
SECONDARY OBJECTIVES:
I. To compare overall response rates (ORR) in WM participants treated upfront with IR vs. those treated with VR.
II. To compare progression-free survival (PFS), time to next treatment, duration of response in WM participants treated upfront with IR vs. those treated with VR.
III. To compare the rate of complete response (CR) in WM participants treated upfront with IR vs. those treated with VR.
IV. To evaluate the safety of the IR regimen as compared to VR regimen in participants with WM.
V. To evaluate the time to VGPR in WM participants treated upfront with IR and those treated with VR.
VI. To evaluate the ORR in participants who progress on treatment with IR and VR and are crossed over to the other respective arm.
VII. To compare overall survival (OS) in WM participants treated upfront with IR vs. those treated with VR.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of cycles 1-24 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycles 2 and 5. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm I may receive rituximab and venetoclax as in Arm II for up to an additional 24 cycles. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
ARM II: Patients receive venetoclax PO QD on days 1-28 of each cycle and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm II may receive ibrutinib and rituximab as in Arm I for up to an additional 24 cycles. Patients undergo CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
After completion of study treatment, patients removed from protocol prior to progression are followed every 3 months until progression, death or 5 years after initial registration, whichever occurs first. Patients followed after progression of disease are followed every 6 months until death or 5 years after initial registration.
I. To compare the rate of very good partial response or better (VGPR or better) in previously untreated participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib plus rituximab (IR) versus (vs.) venetoclax plus rituximab (VR) regimen.
SECONDARY OBJECTIVES:
I. To compare overall response rates (ORR) in WM participants treated upfront with IR vs. those treated with VR.
II. To compare progression-free survival (PFS), time to next treatment, duration of response in WM participants treated upfront with IR vs. those treated with VR.
III. To compare the rate of complete response (CR) in WM participants treated upfront with IR vs. those treated with VR.
IV. To evaluate the safety of the IR regimen as compared to VR regimen in participants with WM.
V. To evaluate the time to VGPR in WM participants treated upfront with IR and those treated with VR.
VI. To evaluate the ORR in participants who progress on treatment with IR and VR and are crossed over to the other respective arm.
VII. To compare overall survival (OS) in WM participants treated upfront with IR vs. those treated with VR.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of cycles 1-24 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycles 2 and 5. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm I may receive rituximab and venetoclax as in Arm II for up to an additional 24 cycles. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
ARM II: Patients receive venetoclax PO QD on days 1-28 of each cycle and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm II may receive ibrutinib and rituximab as in Arm I for up to an additional 24 cycles. Patients undergo CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
After completion of study treatment, patients removed from protocol prior to progression are followed every 3 months until progression, death or 5 years after initial registration, whichever occurs first. Patients followed after progression of disease are followed every 6 months until death or 5 years after initial registration.
Study Oversight
Has Oversight DMC:
False
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-2021-02851 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| S2005 | OTHER | SWOG | View | |
| S2005 | OTHER | CTEP | View | |
| U10CA180888 | NIH | None | https://reporter.nih.gov/quic… | View |