Tafasitamab + Zanubrutinib for Chronic Lymphocytic Leukemia

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers

Disqualifiers: Hepatitis B, HIV, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two treatments, tafasitamab and zanubrutinib, for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Tafasitamab, a monoclonal antibody, may inhibit cancer cell growth and spread, while zanubrutinib blocks signals that prompt cancer cells to multiply. The trial aims to determine if using both treatments together can eliminate more cancer cells than using them separately. This trial may suit those newly diagnosed with CLL/SLL who have not received previous treatments, except for steroids or rituximab, and who experience severe symptoms like extreme fatigue or significant weight loss. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use certain medications like strong CYP3A4 inducers within 2 weeks before starting the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the FDA approved tafasitamab, indicating it passed strict tests for safety and effectiveness in other conditions. This approval suggests tafasitamab is generally well-tolerated.

Studies have found zanubrutinib to be easier on the body than similar drugs like ibrutinib, causing fewer side effects that lead to treatment discontinuation and fewer heart-related issues.

Although specific safety data on using tafasitamab and zanubrutinib together is not available, these findings suggest both drugs are relatively safe on their own. Participants in this clinical trial might experience side effects, but the known safety records of these drugs provide reassurance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about tafasitamab and zanubrutinib for chronic lymphocytic leukemia because these treatments offer a fresh approach compared to standard therapies like chemotherapy and targeted inhibitors. Tafasitamab is a monoclonal antibody that targets CD19, a protein found on the surface of cancerous B-cells, enhancing the immune system's ability to attack the cancer. Zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that disrupts cancer cell survival signals more selectively, potentially leading to fewer side effects. Together, these treatments provide a novel one-two punch that could improve outcomes for patients by directly targeting cancer cells while also boosting the body's natural defenses.

What evidence suggests that tafasitamab and zanubrutinib might be an effective treatment for chronic lymphocytic leukemia?

Research has shown that using tafasitamab and zanubrutinib together might be more effective at killing cancer cells in people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) than using either drug alone. In this trial, participants will receive both tafasitamab and zanubrutinib. Tafasitamab is already approved for treating another type of cancer and has a 55% success rate in those cases. Zanubrutinib has shown promise for CLL, especially for patients who can't handle other treatments. These two drugs might work better together because tafasitamab helps stop cancer cells from growing, while zanubrutinib blocks signals that make cancer cells multiply. Early results suggest this combination could be a strong option for people newly diagnosed with CLL or SLL. ^{1 3 4 5 6}

Who Is on the Research Team?

Matthew Mei, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma who need treatment and can swallow pills. They should have no prior CLL treatments (except certain steroids/rituximab), stable organ function, and no severe bleeding disorders or liver disease. Participants must agree to use birth control and not be pregnant.

Inclusion Criteria

My kidneys work well enough, with a clearance rate of at least 30 mL/min.

My blood clotting measurements are within safe limits, with or without anticoagulants.

I can perform all my self-care activities and am up more than 50% of my waking hours.

Exclusion Criteria

History of prior malignancy except: Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study, Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease, Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease, Asymptomatic prostate cancer managed with 'watch and wait' strategy, Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions), Known positive test result for SARS-CoV-2 unless follow-up test was negative or investigator deems the infection is fully resolved, Known positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing) and a positive test result for HCV ribonucleic acid (RNA). Participants with positive serology are eligible in case of negative HCV RNA test results, Known positive test result for chronic hepatitis B virus (HBV) infection (defined by hepatitis B virus surface antigen [HBsAg] positivity), Participants with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody) may be included if HBV deoxyribonucleic acid (DNA) was undetectable, provided that they are willing to undergo ongoing DNA testing, Antiviral prophylaxis may be administered as per institutional guidelines, Participants who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible, Known seropositive for or history of active viral infection with human immunodeficiency virus (HIV), Clinically significant cardiovascular disease including the following: Myocardial infarction within 6 months before screening, Unstable angina within 3 months before screening, New York Heart Association class III or IV congestive heart failure, History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes), QTcF > 480 milliseconds based on Fridericia's formula, History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place, Known severe chronic obstructive pulmonary disease (COPD), Known hepatic cirrhosis or severe pre-existing hepatic impairment, Major surgery (requiring general anesthesia) within 14 days before the first dose of study drug or a scheduled surgery during study period, Patients with clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting or any other condition that will interfere significantly with drug absorption, Females only: Pregnant or breastfeeding, Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures, Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

I have not had major surgery in the last 30 days.

I take more than 20 mg/day of prednisone or its equivalent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Evaluation of the safety and tolerability of tafasitamab and zanubrutinib

4 weeks

Weekly visits for safety assessments

Treatment

Patients receive tafasitamab IV and zanubrutinib PO, with blood samples, CT scans, and bone marrow biopsies conducted throughout the trial

24 months

Monthly visits for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Bi-annual visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Tafasitamab
• Zanubrutinib

Trial Overview The trial is testing the combination of tafasitamab, a monoclonal antibody, and zanubrutinib, a kinase inhibitor protein blocker, in treating newly diagnosed patients. It aims to see if this combo is more effective than individual treatments for stopping cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (tafasitamab and zanubrutinib) Experimental Treatment 5 Interventions

Patients receive tafasitamab IV and zanubrutinib PO on study. Patients also undergo collection of blood samples on study and undergo CT scan and bone marrow biopsy throughout the trial.

Tafasitamab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, in adult patients who are not eligible for autologous stem cell transplant

Approved in European Union as Minjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients who are not eligible for autologous stem cell transplant

Approved in Canada as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Zanubrutinib demonstrated a high overall response rate of 95.4% in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, with treatment-naïve patients showing even better outcomes (100% response) compared to those with relapsed/refractory disease (91.0%).

The long-term follow-up indicated that earlier treatment with zanubrutinib leads to significantly longer progression-free and overall survival, while maintaining a favorable safety profile, with serious adverse events primarily being infections and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Xu, W., Yang, S., Tam, CS., et al.[2022]

In the phase 3 SEQUOIA trial involving adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to the standard treatment of bendamustine plus rituximab (BR).

Patients treated with zanubrutinib reported better health-related quality-of-life outcomes at 12 and 24 weeks, including improvements in global health status, physical functioning, and reduced symptoms of diarrhea, fatigue, and nausea/vomiting compared to those receiving BR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. Ghia, P., Barnes, G., Yang, K., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, showed a high overall response rate of 94.5% in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma carrying the del(17p) mutation, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with an estimated 18-month progression-free survival rate of 88.6% and an overall survival rate of 95.1%, although some patients experienced adverse events, including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Tam, CS., Robak, T., Ghia, P., et al.[2021]

Zanubrutinib, a selective BTK inhibitor, was well-tolerated in a phase 1 study with 144 patients, showing no dose-limiting toxicities and achieving over 95% BTK occupancy in blood cells at all tested doses.

In patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib demonstrated a remarkable overall response rate of 96.2% and a 100% estimated progression-free survival at 12 months, indicating strong efficacy with low major toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Tam, CS., Trotman, J., Opat, S., et al.[2021]

In a phase 3 study involving 590 patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating a strong efficacy advantage.

Zanubrutinib demonstrated an acceptable safety profile, with fewer severe adverse events like neutropenia compared to bendamustine-rituximab, suggesting it could be a promising new treatment option for patients with CLL and SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Tam, CS., Brown, JR., Kahl, BS., et al.[2023]

In a phase 3 trial involving 652 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib demonstrated superior progression-free survival compared to ibrutinib, with a hazard ratio of 0.65, indicating a significant reduction in the risk of disease progression or death.

Zanubrutinib also had a better safety profile than ibrutinib, resulting in fewer adverse events that led to treatment discontinuation, particularly fewer cardiac events, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. Brown, JR., Eichhorst, B., Hillmen, P., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, was found to be generally well tolerated when combined with obinutuzumab in a phase 1 study involving 81 patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

The combination therapy showed high efficacy, achieving a 100% overall response rate in treatment-naïve CLL patients and a 92% response rate in relapsed/refractory CLL patients, with a 72% response rate in relapsed/refractory FL patients over a median follow-up of 20 to 29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Tam, CS., Quach, H., Nicol, A., et al.[2021]

Zanubrutinib (zanu) has been shown to significantly improve progression-free survival compared to bendamustine-rituximab in treatment-naive patients with chronic lymphocytic leukemia (CLL), indicating its efficacy as a first-line treatment option.

In a direct comparison with ibrutinib, zanu demonstrated a better safety profile and enhanced clinical efficacy, leading to its approval by the FDA and EMA as a preferred treatment for CLL/SLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option. Molica, S., Tam, C., Allsup, D., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05718869

Tafasitamab and Zanubrutinib for the Treatment of Patients ... Giving tafasitamab and zanubrutinib in combination may kill more cancer cells in patients with CLL/SLL than giving either treatment alone. Detailed Description.

2. oncodaily.com oncodaily.com/drugs/tafasitamab-cxix-monjuvi-patient-version

Tafasitamab-cxix (Monjuvi): What Patients Need to Know ... Efficacy and Results from Clinical Trials. The FDA's 2020 approval for DLBCL came from the L-MIND study, which showed a 55% overall response ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/14656566.2023.2229734

Zanubrutinib for the treatment of chronic lymphocytic ... This data suggests that Zanubrutinb could be the perfect treatment option for high-risk patients who results intolerant to other BTKis. Nowadays, the exact role ...

4. iwcll2025.org iwcll2025.org/PosterTitles.asp?PosterSortOrder=num&pfp=Browse%20by%20Poster%20Title

Abstract Listing A Phase 2 study with Tafasitamab and Zanubrutinib in newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma – TaZa CLL Study.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10929554/

Taking the Next Step in Double Refractory Disease Outcomes for Patients With Chronic Lymphocytic Leukemia (CLL) previously treated with both a covalent BTK and BCL2 Inhibitor in the United ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10205

Tafasitamab and Zanubrutinib for the Treatment of Patients ... Giving tafasitamab and zanubrutinib in combination may kill more cancer cells in patients with CLL/SLL than giving either treatment alone. Eligibility Criteria ...