Autoimmune Hemolytic AnemiaPhase 2NCT04657094
Acalabrutinib for the Treatment of Relapsed or Refractory Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia
A Phase 2 study testing Acalabrutinib in people with Autoimmune Hemolytic Anemia and Chronic Lymphocytic Leukemia, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Hemolytic Anemia, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- What is being tested?
- Acalabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2021to 8 Feb 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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)
- Alanine aminotransferase (ALT) =< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy)
- Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 30 days prior to day 1 of protocol therapy)
- If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (prothrombin time [PT]) < 2 x ULN (within 30 days prior to day 1 of protocol therapy). If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (within 30 days prior to day 1 of protocol therapy)
- If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) < 2 x ULN (within 30 days prior to day 1 of protocol therapy). If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (within 30 days prior to day 1 of protocol therapy)
- Seronegative for human immunodeficiency virus (HIV) Ag/Ab combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 30 days prior to day 1 of protocol therapy)
- If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within the screening window prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by females of childbearing potential to use highly effective methods of birth control or abstain from heterosexual activity starting with the first dose of study therapy through 2 days after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Who cannot join
- 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)
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- 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
- Inadequate recovery from adverse events related to prior therapy to grade 1 or baseline (excluding grade 2 alopecia and neuropathy)
- Active uncontrolled infection
- Known history of immunodeficiency virus (HIV) infection
- Subjects who have an undetectable or unquantifiable HIV viral load with CD4 > 300 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
- Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Participants who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Note that intravenous immunoglobulin therapy (IVIG) administration may lead to positive anti-HBc test result
- Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
- Major surgery (requiring general anesthesia) within 28 days prior to initiation of therapy
- Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- History of prior malignancy except:
- Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study
- Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
- Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease
- Asymptomatic prostate cancer managed with "watch and wait" strategy
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) =< 40%
- Psychiatric illness/social situations that would limit compliance with study requirements
- Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Phase 2 Trial of Acalabrutinib for the Treatment of Relapsed/Refractory Autoimmune Hemolytic Anemia
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.
Read the detailed description
PRIMARY OBJECTIVE:
- Assess the efficacy of acalabrutinib in chronic lymphocytic leukemia (CLL) patients with relapsed or refractory autoimmune hemolytic anemia (AIHA).
SECONDARY OBJECTIVES:
- Evaluate acalabrutinib's ability to induce short term and sustained hemoglobin response.
II. Assess the toxicity of acalabrutinib. III. Evaluate efficacy of acalabrutinib in CLL.
EXPLORATORY OBJECTIVE:
- Assess the effect of acalabrutinib on T-cell functionality in an autoimmune disorder.
OUTLINE:
Patients receive acalabrutinib orally (PO) twice daily (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.
After completion of study treatment, patients are followed up at 30 days and at least every 4 months for up to 12 months.
- Conditions
- Autoimmune Hemolytic Anemia, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Warm Antibody Autoimmune Hemolytic Anemia
- Being tested
- Acalabrutinib
- Medical subject headings
- Anemia, Hemolytic, Autoimmune, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Participants were assessed at the end of the 6-week therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start16 Mar 2021
- Primary completion1 Apr 2023
- Study completion8 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autoimmune Hemolytic AnemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Alexey Danilov, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04657094
- Sponsor's protocol ID
- 20311
- Other IDs
- NCI-2020-10529, 20311, P30CA033572
- Status last verified
- Apr 2026
- First submitted
- 1 Dec 2020
- Last updated
- 6 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Acalabrutinib for the Treatment of Relapsed/Refractory Autoimmune Hemolytic Anemia
- ClinicalTrials.gov ID
- NCT04657094
- Acronym / sponsor ID
- 20311
- Conditions
- Autoimmune Hemolytic Anemia, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Warm Antibody Autoimmune Hemolytic Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 4 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Mar 2021 (actual)
- Primary completion
- 1 Apr 2023 (actual)
- Study completion
- 8 Feb 2027 (estimated)
- First posted
- 8 Dec 2020 (actual)
- Results
- Posted 29 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- Assess the efficacy of acalabrutinib in chronic lymphocytic leukemia (CLL) patients with relapsed or refractory autoimmune hemolytic anemia (AIHA).
SECONDARY OBJECTIVES:
- Evaluate acalabrutinib's ability to induce short term and sustained hemoglobin response.
II. Assess the toxicity of acalabrutinib. III. Evaluate efficacy of acalabrutinib in CLL.
EXPLORATORY OBJECTIVE:
- Assess the effect of acalabrutinib on T-cell functionality in an autoimmune disorder.
OUTLINE:
Patients receive acalabrutinib orally (PO) twice daily (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.
After completion of study treatment, patients are followed up at 30 days and at least every 4 months for up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (acalabrutinib) | Experimental | Drug: AcalabrutinibPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Documented informed consent of the participant and/or legally authorized representative
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- 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:
- 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
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, CalquenceGiven PO | Drug | Treatment (acalabrutinib) |
Primary outcome
Autoimmune Hemolytic Anemia (AIHA) - Overall Response Rate (ORR)
Time frame: Participants were assessed at the end of the 6-week therapy.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Autoimmune Hemolytic Anemia
Active, not recruitingPhase 1
A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia, Anti-CD19 STAR T-cell Therapy
Not yet recruitingPhase 1
IASO206 in Patients With Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia, Relapsed/Refractory
Active, not recruitingPhase 1
CAR T-cell Therapy Targeting CD19 and BCMA in Patients With AIHA Who Have Failed ≥3 Lines of Therapy.
Autoimmune Hemolytic Anemia, CD19/BCMA CAR T-cells
RecruitingObservational study
Brain Function and Psychological Changes Related to Cell Therapy for Autoimmune Hemolytic Anemia
CAR T-cell Therapy, Autoimmune Hemolytic Anemia
RecruitingPhase 1
F182112 in Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexey Danilov principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib in people with Autoimmune Hemolytic Anemia and Chronic Lymphocytic Leukemia, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autoimmune Hemolytic Anemia (AIHA) - Overall Response Rate (ORR) (time frame: Participants were assessed at the end of the 6-week therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.