Loncastuximab + Acalabrutinib for Chronic Lymphocytic Leukemia

Overseen By Pamela M Hardwick

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayur Narkhede

Must be taking: Acalabrutinib

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, CNS involvement, Heart failure, others

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

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

Compensation: Varies

Number of Visits: 12

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of two drugs, Loncastuximab Tesirine (an antibody-drug conjugate) and Acalabrutinib (a targeted therapy known as a Bruton's tyrosine kinase inhibitor), for treating chronic lymphocytic leukemia (CLL). CLL is a blood cancer affecting white blood cells. Researchers will test various dose levels of Loncastuximab alongside a consistent dose of Acalabrutinib to assess patient tolerance. Individuals with CLL who are currently taking Acalabrutinib without recent progression and have undergone at least one previous treatment may qualify for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that participants have been on acalabrutinib for at least 3 months, so you will need to continue taking it. The protocol does not specify if you need to stop other medications, but you cannot be on certain immunosuppressive drugs or high doses of corticosteroids.

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

Research shows that both Loncastuximab Tesirine and Acalabrutinib have been used to treat blood cancers. Acalabrutinib is already approved for chronic lymphocytic leukemia (CLL). In past studies, common side effects included low red blood cells (anemia), low white blood cells (neutropenia), and headaches, occurring in about 30% of patients.

Loncastuximab Tesirine has been used for relapsed or refractory large B-cell lymphoma. While its side effects for CLL are less known, it has been studied in other blood cancers.

This trial is in an early phase, focusing on finding the best dose and ensuring safety. Researchers closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for chronic lymphocytic leukemia (CLL) involve targeting the cancer cells directly or boosting the immune system. However, Loncastuximab Tesirine combined with Acalabrutinib offers a unique approach. Loncastuximab Tesirine is an antibody-drug conjugate, which means it combines an antibody that specifically targets cancer cells with a toxic drug that kills them once inside. This targeted delivery helps to minimize damage to healthy cells. Acalabrutinib, on the other hand, is a Bruton’s tyrosine kinase (BTK) inhibitor, which disrupts the cancer cell signaling, slowing their growth. Researchers are excited because this combination could offer a more precise and effective treatment option for CLL, potentially leading to better outcomes with fewer side effects.

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

In this trial, participants will receive a combination of acalabrutinib and loncastuximab tesirine at varying dose levels. Previous studies have shown that acalabrutinib effectively treats chronic lymphocytic leukemia (CLL). The FDA has approved it as a first treatment option and for patients who have tried other treatments. This medication blocks a protein that aids cancer cell growth. Loncastuximab tesirine combines an antibody with a chemotherapy drug, delivering the drug directly to cancer cells. By combining these treatments, the goal is to target leukemia cells more effectively. Early research suggests that this combination could improve treatment outcomes for CLL patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Aditi Saha, M.D.

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for people with chronic lymphocytic leukemia (CLL) who have been on Acalabrutinib for at least 3 months without disease progression. Participants must have had prior CLL treatment, measurable residual disease, and adequate kidney and liver function. They should not be using G-CSF within 7 days of joining the study.

Inclusion Criteria

I've been on acalabrutinib for 3+ months with no cancer progression.

My leukemia cells show specific markers that indicate CLL.

My liver functions within normal ranges, or I have Gilbert's Disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Loncastuximab Tesirine and Acalabrutinib for up to 12 cycles to determine the maximum tolerated dose

36 weeks

12 visits (in-person, every 21 days)

Dose-Limiting Toxicity Evaluation

Evaluation of dose-limiting toxicities over two cycles to determine the maximum tolerated dose

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Loncastuximab Tesirine

Trial Overview The study aims to find the highest dose of Loncastuximab Tesirine that can be safely added to Acalabrutinib in treating CLL without causing severe side effects. It's an early-phase trial focusing on dosage levels.

How Is the Trial Designed?

Group I: Dose level 4: Experimental Treatment 1 Intervention

90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent 10 cycles) + Acalabrutinib 100 mg BID for a total of 12 cycles.

Group II: Dose Level 3 Experimental Treatment 1 Intervention

75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

Group III: Dose Level 2 Experimental Treatment 1 Intervention

60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

Group IV: Dose Level 1: Experimental Treatment 1 Intervention

45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles

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

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Mayur Narkhede

Lead Sponsor

Trials

1

Recruited

20+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05971251

Study Details | NCT05971251 | Addition of Loncastuximab ... Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab Tesirine to Aclabrutinib in the treatment of chronic lymphocytic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40736551/

Real-world efficacy and safety outcomes of acalabrutinib in ... Real-world efficacy and safety outcomes of acalabrutinib in chronic lymphocytic leukemia: primary results of a French multicentre observational ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03414

LoncastuxImab Tesirine and Acalabrutinib for the ... This phase I trial tests the safety, side effects, and best dose of loncastuxlmab tesirine with acalabrutinib in treating patients with chronic lymphocytic ...

4. calquence.com calquence.com/why-calquence/how-effective-calquence-cll.html

How Effective Is CALQUENCE® (acalabrutinib)? | CLL Based on clinical trials, the FDA has determined that CALQUENCE is safe and effective as a first-line CLL/SLL treatment (or second-line or beyond).

5. withpower.com withpower.com/trial/phase-1-leukemia-7-2023-8e182

Loncastuximab + Acalabrutinib for Chronic Lymphocytic ... This trial is for people with chronic lymphocytic leukemia (CLL) who have been on Acalabrutinib for at least 3 months without disease progression. Participants ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/210259s011lbl.pdf

Reference ID: 5512932 - accessdata.fda.gov The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract ...

7. resources.massgeneralbrighamhealthplan.org resources.massgeneralbrighamhealthplan.org/pharmacy/PharmacyPolicies/Medicaid/LymphomaLeukemiaAgents_ArzerraGazyvaZynlonta_PA_MH_MB_06.01.25.pdf

Lymphoma and Leukemia Agents Arzerra (ofatumumab ... Zynlonta (loncastuximab) is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/216387s004lbl.pdf

Clinical Trials - accessdata.fda.gov The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract ...

9. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2019/calquence-data-to-show-improved-progression-free-survival-in-phase-iii-front-line-chronic-lymphocytic-leukaemia-trial-at-ash-2019-annual-meeting.html

Calquence data to show improved progression-free ... AstraZeneca will present the first data from the Phase III ELEVATE-TN trial assessing Calquence (acalabrutinib), a next-generation selective Bruton's tyrosine ...