Sonrotoclax + Rituximab + Zanubrutinib for Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen ByMazyar Shadman, MD, MPH

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Fred Hutchinson Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This phase II trial studies the side effects of an escalated ramp-up of sonrotoclax following initial debulking with zanubrutinib or rituximab in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL) that is newly diagnosed, has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill tumor cells. Zanubrutinib may stop the growth of tumor cells by blocking a protein called Bruton's tyrosine kinase (BTK), which is needed for tumor cell growth. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. Giving an increased dose of sonrotoclax over a shorter period of time in combination with zanubrutinib or rituximab may be safe and tolerable in treating patients with newly diagnosed, relapsed or refractory CLL, SLL, and MCL.

Eligibility Criteria

This trial is for adults over 18 with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL) that's new, returned, or resistant to treatment. They must meet specific health criteria and agree to use effective contraception. Excluded are those with certain medical conditions, recent major surgery, severe bleeding disorders, active infections needing therapy, known HIV/HBV/HCV infection, inability to swallow capsules or comply with the study.

Inclusion Criteria

I am 18 years old or older.

I have been diagnosed with CLL/SLL or MCL according to WHO guidelines.

I can take care of myself and am up and about more than half of the day.

I am not pregnant and will use effective birth control.

Exclusion Criteria

I have a severe bleeding disorder or a history of spontaneous bleeding that needed treatment.

I have a history of lung, autoimmune, liver diseases, or heart rhythm issues.

I am not taking any medication known to affect heart rhythm nor have I recently received a live vaccine.

My lymphoma/leukemia has spread to my brain or spinal cord.

I have had certain blood cancer or a stem cell transplant.

I am currently on medication for an infection.

I have been diagnosed with HIV, HBV, or HCV.

I am not pregnant, breastfeeding, and can swallow capsules.

Participant Groups

The trial tests an escalated dose of Sonrotoclax after initial treatment with Zanubrutinib or Rituximab in patients with CLL/SLL/MCL. It aims to determine if this combination is safe and tolerable when increasing Sonrotoclax dosage quickly. The drugs target proteins essential for tumor cell survival and growth.

2Treatment groups

Experimental Treatment

Group I: Treatment (zanubrutinib + sonrotoclax)Experimental Treatment6 Interventions

Patients not refractory to a BTKi undergo debulking and receive zanubrutinib PO QD on day 1 of cycles 1-15. Beginning on day 1 of cycle 4, patients receive a ramp up of sonrotoclax PO QD until target dose is reached. Patients who tolerate receiving sonrotoclax continue to receive sonrotoclax together with zanubrutinib PO QD for all subsequent cycles. Cycles repeat every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT during screening and on study and blood sample collection throughout the study. Additionally, patients may undergo bone marrow biopsy and endoscopy on study.

Group II: Treatment (rituximub + sonrotoclax)Experimental Treatment6 Interventions

Patients who are refractory to a BTKi undergo debulking and receive rituximab PO QD on days 1, 8, 15, and 22 of 1 cycle. Beginning on day 1 of cycle 2, patients receive a ramp up of sonrotoclax PO QD until target dose is reached. Patients will continue sonrotoclax PO QD through cycle 13. Patients also continue to receive ritiximab PO QD on day 1 of cycles 3-6. Cycles repeat every 28 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT during screening and on study and blood sample collection throughout the study. Additionally, patients may undergo bone marrow biopsy and endoscopy on study.