Tafasitamab + Acalabrutinib + Venetoclax for Chronic Lymphocytic Leukemia

Not yet recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers

Disqualifiers: Chronic corticosteroids, Major surgery, Active infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 14 cycles (each cycle is 4 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether combining three medications—tafasitamab, acalabrutinib, and venetoclax—can safely and effectively treat chronic lymphocytic leukemia (CLL) and small cell lymphoma (SLL). Each drug works differently to help the immune system target and kill cancer cells or stop them from growing. The trial seeks participants with an active form of CLL/SLL that hasn't been treated before, except with steroids or rituximab for related issues, and who experience symptoms like unintentional weight loss, extreme fatigue, or night sweats. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in CLL/SLL treatment.

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

Research has shown that the combination of tafasitamab, acalabrutinib, and venetoclax is promising in terms of safety for people with certain blood cancers. An earlier study found that patients taking tafasitamab with venetoclax experienced manageable side effects, indicating good tolerability. Additionally, the FDA has already approved acalabrutinib and venetoclax for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), which supports their safety.

Another study found that over 90% of patients using acalabrutinib and venetoclax successfully lowered their risk of serious side effects like tumor lysis syndrome, a condition where cancer cells break down too quickly. This suggests that these drugs are generally well-tolerated and effective when used together.

Overall, while each treatment can cause side effects, existing data supports the safety of this combination for treating CLL and SLL. However, potential trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tafasitamab, Acalabrutinib, and Venetoclax for treating Chronic Lymphocytic Leukemia (CLL) because it brings together three powerful mechanisms of action. Tafasitamab is a monoclonal antibody that targets CD19, a protein on the surface of cancer cells, promoting their destruction. Acalabrutinib is a Bruton’s tyrosine kinase inhibitor that disrupts signals needed for the cancer cells to grow and survive. Venetoclax targets BCL-2, a protein that helps cancer cells avoid death, effectively inducing apoptosis. Together, this combination could potentially offer a more robust attack on CLL compared to standard treatments like chemo-immunotherapy or single-agent targeted therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Studies have shown that combining acalabrutinib and venetoclax holds promise for treating chronic lymphocytic leukemia (CLL). In one study, patients using this combination maintained stable cancer for three years, meaning it did not worsen during that period. Tafasitamab, when paired with venetoclax, also produced positive results, with some patients showing no detectable signs of cancer in their blood. Each drug functions differently: tafasitamab aids the immune system in attacking cancer cells, acalabrutinib inhibits cancer cell growth, and venetoclax helps kill cancer cells. This trial will evaluate the combination of tafasitamab, acalabrutinib, and venetoclax, potentially offering a robust defense against CLL. ^{1 2 4 6 7}

Who Is on the Research Team?

Benjamin M Heyman

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Participants should be able to safely receive the study drugs and procedures, as determined by their doctor. Specific inclusion and exclusion criteria apply.

Inclusion Criteria

I am 18 years old or older.

Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines

Seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV) with undetectable viral load for eligibility

Exclusion Criteria

I have had major surgery within the last 30 days.

Positive test results for hepatitis C (HCV) and hepatitis B virus (HBV)

Pregnant or breastfeeding females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive acalabrutinib, venetoclax, and tafasitamab over multiple cycles with varying administration schedules

14 cycles (each cycle is 4 weeks)

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 3 months until progression, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Tafasitamab
• Venetoclax

Trial Overview

The study is testing a combination of three medicines—tafasitamab, acalabrutinib, and venetoclax—to see if they are safe and effective in treating CLL/SLL. Patients will also have imaging scans and lab tests during the trial.

How Is the Trial Designed?

Group I: Treatment (Tafasitamab, acalabrutinib, venetoclax) Experimental Treatment 7 Interventions

See Detailed Description

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+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07582159

Tafasitamab With Acalabrutinib and Venetoclax for the ...

This phase II trial tests the safety, side effects and how well giving tafasitamab with acalabrutinib and venetoclax works for the treatment ...

2.

onclive.com

onclive.com/view/efficacy-and-safety-of-first-line-acalabrutinib-plus-venetoclax-revamps-qol-outcomes-in-cll

Efficacy and Safety of First-Line Acalabrutinib Plus ...

Data from the trial showed that patients in the acalabrutinib-plus-venetoclax arm (n = 291) achieved a 3-year progression-free survival (PFS) ...

3.

tandfonline.com

tandfonline.com/doi/full/10.1080/10428194.2021.1964020

Tafasitamab combined with idelalisib or venetoclax in ...

Undetectable minimal residual disease in peripheral blood was achieved in 2/8 patients (cohort A) and 6/7 patients (cohort B). Overall, these results suggest ...

4.

iwcll.org

iwcll.org/work/biennial-meetings/iwcll-xxi-biennial-meeting-2025/2025-poster-gallery/real-world-treatment-outcomes-among-patients-with-high-risk-cll-sll-receiving-venetoclax-based-therapy-in-1l-or-2l-an-updated-international-study/

Real-world Treatment Outcomes among Patients with High ...

Real-world Treatment Outcomes among Patients with High-Risk CLL/SLL Receiving Venetoclax-Based Therapy in 1L or 2L: An Updated International Study.

5.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-venetoclax-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma

FDA approves acalabrutinib with venetoclax for chronic ...

The median duration of PFS follow-up was 42.6 months. Median PFS was not estimable (NE) (95% CI: 51.1, NE) in the AV arm and 47.6 months (95% CI ...

6.

iwcll.org

iwcll.org/work/biennial-meetings/iwcll-xxi-biennial-meeting-2025/2025-poster-gallery/safety-analysis-of-fixed-duration-acalabrutinib-venetoclax-combinations-vs-chemoimmunotherapy-a-post-hoc-analysis-from-the-phase-3-amplify-trial/

Safety Analysis of Fixed-Duration Acalabrutinib-Venetoclax ...

Over 90% of patients at high TLS risk at baseline transitioned to low/medium risk with initial tumor debulking with 2 cycles of acalabrutinib lead-in. Keywords ...

7.

prnewswire.com

prnewswire.com/news-releases/us-food-and-drug-administration-fda-approves-combination-treatment-of-venclexta-venetoclax-and-acalabrutinib-for-previously-untreated-patients-with-chronic-lymphocytic-leukemia-cll-302693421.html

U.S. Food and Drug Administration (FDA) Approves ...

Study results showed the combination regimen of VENCLEXTA and acalabrutinib reduced the risk of disease progression or death by 35% versus ...