Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

Conditions

• Lymphoplasmacytic Lymphoma
• Waldenstrom Macroglobulinemia

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow biopsy and aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy and aspiration
• Computed Tomography — PROCEDURE
  Undergo CT or PET/CT
• Ibrutinib — DRUG
  Given PO
• Positron Emission Tomography — PROCEDURE
  Undergo PET/CT
• Rituximab — BIOLOGICAL
  Given IV
• Venetoclax — DRUG
  Given PO
• Zanubrutinib — DRUG
  Given PO

Study Details

This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab or zanubrutinib 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. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called BTK, which may help keep cancer cells from growing. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib with rituximab or zanubrutinib alone.

Key Dates

Start date

Jan 5, 2022

Status verified

Mar 2026

Primary completion

Mar 31, 2028

Completion

Mar 31, 2028

Study Design

Enrollment

92 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm I (ibrutinib + rituximab or zanubrutinib)
  Patients receive ibrutinib PO QD on days 1-28 of cycles 1-24 and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 5, or zanubrutinib PO QD or BID on days 1-28 of cycles 1-24. 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 CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
• Experimental: Arm II (venetoclax, rituximab)
  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. 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 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.

Primary Outcome Measure

Very good partial response or better (VGPR or better) rate [ Time Frame: Up to 5 years ]

Locations (131)

Find similar trials in Tucson, AZ

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