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

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies acalabrutinib, a medication that may help stop cancer cell growth in patients with chronic lymphocytic leukemia and certain types of anemia. The medication works by blocking enzymes essential for cancer cell growth.

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.

What data supports the effectiveness of the drug Acalabrutinib for treating autoimmune hemolytic anemia in chronic lymphocytic leukemia?

Acalabrutinib has been shown to be effective in treating chronic lymphocytic leukemia (CLL) by targeting a specific protein involved in the disease's progression, leading to longer periods without disease worsening. It is generally well-tolerated and has a favorable safety profile compared to other similar drugs, which suggests it could be beneficial for related conditions like autoimmune hemolytic anemia in CLL patients. ^{1 2 3 4 5}

Is acalabrutinib safe for humans?

Acalabrutinib has been shown to have a generally favorable safety profile in patients with chronic lymphocytic leukemia, with common side effects including headache, diarrhea, and infections. However, it may increase the risk of certain conditions like neutropenia (low white blood cell count) and cardiac events such as atrial fibrillation (irregular heartbeat). ^{1 2 4 6 7}

How is the drug Acalabrutinib unique for treating autoimmune hemolytic anemia in chronic lymphocytic leukemia?

Acalabrutinib is unique because it is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein involved in the growth and survival of cancer cells, potentially reducing side effects compared to less selective treatments. It has shown improved safety outcomes in chronic lymphocytic leukemia, making it a promising option for patients with autoimmune hemolytic anemia in this context. ^{1 2 3 4 8}

Research Team

Alexey Danilov

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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'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 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]

References

1. United States 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. [2021]

2. United States 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. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

5. Spain pubmed.ncbi.nlm.nih.gov

An update on acalabrutinib to treat chronic lymphocytic leukemia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Acalabrutinib-Related Cardiac Toxicities in Patients with Chronic Lymphocytic Leukemia: A Meta-Analysis of Randomized Controlled Trials. [2022]

7. England 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. [2022]

8. England 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. [2021]