Acalabrutinib for Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Anticancer antibodies, BTK inhibitors

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of acalabrutinib for individuals with chronic lymphocytic leukemia (CLL) who also have a persistent type of anemia (low red blood cells). Acalabrutinib blocks specific enzymes that cancer cells need to grow. Individuals with CLL and anemia that did not improve after treatments like prednisone may be suitable candidates for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that patients on stable chronic AIHA treatments can continue if the dose hasn't changed in the 4 weeks before joining. Some medications, like strong CYP3A4 inducers/inhibitors and proton pump inhibitors, should be avoided or switched.

Is there any evidence suggesting that acalabrutinib is likely to be safe for humans?

Research shows that acalabrutinib is generally safe and well-tolerated by people with chronic lymphocytic leukemia (CLL). In studies with patients whose CLL has returned, acalabrutinib demonstrated a promising safety record, with most participants experiencing only mild to moderate side effects.

A large study in Europe examined acalabrutinib in real-world settings for CLL patients. It found that the safety results aligned with earlier research, with no unexpected issues. Most side effects were manageable and not severe.

Although the treatment remains under study, these findings suggest that acalabrutinib is safe enough for further testing. Participants can feel reassured that the trial treatment has undergone previous testing and has been tolerable for many people with similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Acalabrutinib is unique because it targets Bruton's tyrosine kinase (BTK), a critical enzyme in the pathway that often drives autoimmune hemolytic anemia in chronic lymphocytic leukemia (CLL) patients. Unlike standard treatments like steroids or rituximab, which broadly suppress the immune system, acalabrutinib offers a more targeted approach, potentially reducing side effects associated with generalized immune suppression. Researchers are excited because this precision targeting might improve treatment outcomes, offering a more effective and better-tolerated option for patients with CLL.

What evidence suggests that acalabrutinib might be an effective treatment for autoimmune hemolytic anemia?

Research shows that acalabrutinib, a targeted treatment, may help treat autoimmune hemolytic anemia in people with chronic lymphocytic leukemia (CLL). Studies have found that acalabrutinib can prevent cancer cells from growing by blocking certain necessary enzymes. In patients whose CLL has returned or not responded to other treatments, acalabrutinib has proven safe and effective. Real-world data from Europe also support these findings, showing consistent results in both safety and effectiveness. With these promising results, this trial tests acalabrutinib as a strong option for treating this type of anemia in CLL patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Alexey Danilov

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with chronic lymphocytic leukemia who have autoimmune hemolytic anemia that hasn't improved or has returned after treatment. Participants must be able to swallow pills, not have severe infections like HIV or hepatitis, and women of childbearing age must use effective birth control. People can't join if they've had certain recent treatments, transplants, uncontrolled infections, significant heart issues, are pregnant/breastfeeding, or can't follow the study plan.

Inclusion Criteria

Positive direct antiglobulin test (DAT) (score >= 1+) - either immunoglobulin G (IgG) DAT, C3 DAT, or both. Eligibility of patients with Coombs-negative AIHA should be confirmed by the trial investigator at each respective study site

I have anemia or need treatment to keep my hemoglobin above 10 g/dL.

My diagnosis of CLL or SLL is confirmed by specific lab tests.

Exclusion Criteria

I haven't had radio- or toxin-immunoconjugate therapy in the last 10 weeks.

I cannot swallow pills or have a stomach condition that affects medication absorption.

I haven't received cancer treatment with antibodies in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib orally twice daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles, with a possible extension to 36 cycles.

12-36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with assessments at 30 days and every 4 months for up to 12 months.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib

Trial Overview The trial is testing acalabrutinib's effectiveness in treating relapsed or refractory autoimmune hemolytic anemia in chronic lymphocytic leukemia patients. It's a phase II study looking at how well acalabrutinib blocks enzymes needed for cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (acalabrutinib) Experimental Treatment 1 Intervention

Patients receive acalabrutinib PO BID on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with acalabrutinib may be continued beyond 12 cycles for a maximum of 36 cycles if, in the opinion of the treating physician, the patient might benefit from ongoing therapy.

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?

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

Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.

The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. Delgado, J., Josephson, F., Camarero, J., et al.[2021]

Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.

The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. Davids, MS., Telford, C., Abhyankar, S., et al.[2021]

Acalabrutinib, a Bruton tyrosine kinase inhibitor, showed a 53% overall response rate in patients with relapsed/refractory marginal zone lymphoma, indicating its efficacy in this patient population.

The treatment was generally well tolerated, with a median progression-free survival of 27.4 months and a low incidence of severe adverse events, suggesting improved safety compared to other treatments like ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. Strati, P., Coleman, M., Champion, R., et al.[2022]

In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.

The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Sharman, JP., Egyed, M., Jurczak, W., et al.[2021]

In a phase III study involving 310 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared to investigator's choice treatments, with a median PFS not reached for acalabrutinib versus 16.5 months for the comparator group.

Acalabrutinib demonstrated a favorable safety profile, with serious adverse events occurring in 29% of patients, compared to 56% for idelalisib plus rituximab and 26% for bendamustine plus rituximab, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. Ghia, P., Pluta, A., Wach, M., et al.[2021]

Acalabrutinib, a selective Bruton's tyrosine kinase inhibitor, was found to increase the risk of any-grade cardiac events in patients with chronic lymphocytic leukemia, with a risk ratio of 1.75.

There was a notable trend indicating a higher risk of any-grade atrial fibrillation associated with acalabrutinib, with a risk ratio of 2.56, although no significant increase in hypertension or high-grade cardiac events was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib-Related Cardiac Toxicities in Patients with Chronic Lymphocytic Leukemia: A Meta-Analysis of Randomized Controlled Trials. Htut, TW., Han, MM., Thein, KZ.[2022]

Acalabrutinib, a selective BTK inhibitor, has been FDA approved for treating chronic lymphocytic leukemia (CLL) and shows improved efficacy and safety compared to standard treatments, including ibrutinib.

In multinational phase 1/2 and phase 3 studies, acalabrutinib demonstrated significant effectiveness in treatment-naïve and relapsed refractory CLL patients, with fewer treatment-limiting toxicities such as atrial fibrillation and bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and Its Therapeutic Potential in the Treatment of Chronic Lymphocytic Leukemia: A Short Review on Emerging Data. Isaac, K., Mato, AR.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04657094

Acalabrutinib for the Treatment of Relapsed or Refractory ... This phase II trial studies the effect of acalabrutinib in treating autoimmune hemolytic anemia that has come back (relapsed) or has not responded to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12432023/

Real-world efficacy and safety outcomes of acalabrutinib in ... NAOS, one of the largest real-world cohorts of acalabrutinib-treated CLL patients in Europe, showed effectiveness and safety consistent with ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1509981

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic ... In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with ...

4. withpower.com withpower.com/trial/phase-3-hemolysis-2-2021-6aa18

Acalabrutinib for Autoimmune Hemolytic Anemia in ... Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic ...

5. ashpublications.org ashpublications.org/blood/article/135/15/1204/430030/Acalabrutinib-monotherapy-in-patients-with

Acalabrutinib monotherapy in patients with relapsed/refractory ... At a median follow-up of 41 months, median PFS has not been reached in previously treated CLL patients on the BTK inhibitor acalabrutinib.

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

Real-world efficacy and safety outcomes of acalabrutinib in ... NAOS, one of the largest real-world cohorts of acalabrutinib-treated CLL patients in Europe, showed effectiveness and safety consistent with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04008706

NCT04008706 | Acalabrutinib Safety Study in Untreated ... To evaluate the safety and tolerability of acalabrutinib monotherapy in participants with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8616265/

Autoimmune Hemolytic Anemia in Chronic Lymphocytic ... This review analyzes the occurrence, clinical characteristics, and prognostic impact and treatment of autoimmune hemolytic anemia (AIHA) in chronic lymphocytic ...