Acalabrutinib for the Treatment of Relapsed or Refractory Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia

NCT04657094 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: 20311NCI-2020-10529P30CA033572
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of acalabrutinib in treating autoimmune hemolytic anemia that has come back (relapsed) or has not responded to previous treatment (refractory) in patients with chronic lymphocytic leukemia. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Autoimmune Hemolytic Anemia; Chronic Lymphocytic Leukemia; Warm Antibody Autoimmune Hemolytic Anemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Autoimmune Hemolytic Anemia (AIHA) - Overall Response Rate (ORR)

  ORR is defined as proportion of patients who achieve complete response (CR) and partial response (PR). The probability of having AIHA-ORR at 6 cycles were measured and reported with 95% exact confidence interval (CI). An exact binomial test against a null hypothesis of 30% rate was performed at the 1-sided alpha of 0.05 to determine whether the AIHA-ORR rate at 6 cycles is disappointing or promising.

  Participants were assessed at the end of the 6-week therapy.

Study Arms (1)

Treatment (acalabrutinib)

EXPERIMENTAL

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.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Treatment (acalabrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• "Warm" or "cold" AIHA in patients with CLL, relapsed/refractory (RR) after first line treatment with oral prednisone (with or without rituximab), defined as:
• Anemia (hemoglobin \[Hgb\] =\< 10 g/dL; or Hgb \> 10 g/dL dependent on transfusions or maintenance therapy (rituximab, cyclosporin, etc) to maintain this level of hemoglobin, and
• Laboratory evidence of hemolysis - presence of 3 of 4 markers (increased reticulocyte count, increased indirect bilirubin, increased lactate dehydrogenase, absent haptoglobin)
• 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
• Histologically or flow cytometry confirmed diagnosis of CLL/small lymphocytic lymphoma (SLL)
• Participant must be able to swallow tablets or capsules
• Absolute neutrophil count (ANC) \>= 500/mm\^3 unless due to disease involvement in the bone marrow or autoimmune neutropenia (within 30 days prior to day 1 of protocol therapy)
• Platelets \>= 30,000/mm\^3 unless due to disease involvement in the bone marrow or autoimmune thrombocytopenia (Evans syndrome) (within 30 days prior to day 1 of protocol therapy)
• Direct bilirubin =\< 3.0 x upper limit of normal (ULN) (within 30 days prior to day 1 of protocol therapy)
• Aspartate aminotransferase (AST) =\< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy)

You may not qualify if:

• Therapeutic anticancer antibodies within 3 weeks
• Radio- or toxin-immunoconjugates within 10 weeks
• BH3-mimetic venetoclax, PI3K inhibitors and other "targeted" therapy- within 6 half-lives
• Ibrutinib, acalabrutinib or another BTK inhibitor within 12 months
• Patients on stable chronic AIHA treatments are allowed provided the dose has not changed in the 4 weeks prior to enrollment
• Allogeneic stem cell transplant within 1 year prior to day 1 of protocol therapy, or ongoing immunosuppressive therapy for chronic graft versus host disease (cGVHD)
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
• Strong CYP3A4 inducers/ inhibitors. If the patient requires a strong CYP3A inhibitor/inducer, they should not be enrolled even if it could be held for 14 days before the first dose of study drug
• Proton pump inhibitors (but patients who switch to H2-receptor antagonists or antacids are eligible for enrollment)
• Chronic use of corticosteroids (\> 2 weeks) in excess of prednisone 60 mg/day or its equivalent within 4 weeks prior to start of study therapy. Rescue steroids are allowed during trial
• Vitamin K antagonists
• Known intolerance to acalabrutinib
• History of bleeding disorders or with active bleeding
• Patients with suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• Patients with history of stroke or intracranial hemorrhage within 6 months

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Alexey Danilov
• Organization: City of Hope Medical Center

adanilov@coh.org

6263598111

Study Officials

• Alexey Danilov

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: March 16, 2021
• Primary Completion: April 1, 2023
• Study Completion (Estimated): February 8, 2027
• Last Updated: May 6, 2026
• Results First Posted: May 29, 2024

Record last verified: 2026-04

Locations

US (1)