Zanubrutinib + Odronextamab for Richter's Transformation

Recruiting in Palo Alto (17 mi)

Alexey Danilov, M.D., Ph.D. | City of Hope

Overseen byAlexey V. Danilov

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: City of Hope Medical Center

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and/or effective in treating patients with Richter's transformation.

Research Team

Alexey V. Danilov

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with Richter's transformation, a condition where chronic lymphocytic leukemia changes into an aggressive type of lymphoma. Participants must have specific markers on their cancer cells and be fit enough for biopsies and scans.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ≤ 5 x ULN if attributed to lymphoma involvement of the liver

Sperm donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment

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Exclusion Criteria

I have not received a live vaccine in the last 28 days.

My heart condition is not stable.

Known hypersensitivity to both allopurinol and rasburicase

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Treatment Details

Interventions

Odronextamab (Monoclonal Antibodies)
Zanubrutinib (Tyrosine Kinase Inhibitor)

Trial OverviewThe trial tests zanubrutinib combined with odronextamab in treating Richter's transformation. Zanubrutinib blocks proteins that help cancer grow, while odronextamab targets both B-cells and T-cells to hinder cancer spread.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Treatment (odronextamab, zanubrutinib)Experimental Treatment10 Interventions

Patients receive odronextamab IV over 4 hours on days 1, 2, 8, 9, 15 and 16 of cycle 1 and over 1-4 hours on days 1, 8 and 15 of cycles 2-4 and then on days 1 and 15 of remaining cycles. Patients with CR at cycle 9 may receive odronextamab on day 1 of remaining cycles. Starting with cycle 2, patients also receive zanubrutinib PO QD or BID of each cycle. Cycles repeat every 21 days for cycles 1-4 in the absence of disease progression or unacceptable toxicity then repeat every 28 days for up to cycle 12. After 12 cycles, patients may continue zanubrutinib at investigator's discretion. Patients also undergo ECHO or MUGA and optional bone marrow biopsy at screening and ultrasound guided biopsy of lymph node at screening and during days 2-12 of cycle 2. Additionally, patients undergo blood sample collection and PET, or CT throughout the study.