Chronic Lymphocytic LeukemiaPhase 2NCT04660045
Early Intervention With Acalabrutinib in Patients With High Risk CLL
A Phase 2 study testing Acalabrutinib in people with Chronic Lymphocytic Leukemia and CLL/SLL, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
This study evaluates the effectiveness of acalabrutinib treatment in patients with chronic lymphocytic leukemia (CLL) deemed at high risk for Richter's Transformation (RT). This is a single arm study. Enrolled patients will initiate therapy with acalabrutinib and will dose continuously. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, CLL/SLL
- What is being tested?
- Acalabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2022to Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
- The time from diagnosis to consent should be ≤6 months.
- Subject must be ≥ 18 years of age.
- Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
- Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL guidelines
- Subject must have high risk CLL as defined by any one of the following:
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- NOTCH1 mutated (classic frameshift mutation only)
- Unmutated V4-39 B cell receptor usage
- Pathogenic c-MYC mutations
- Complex karyotype, (by CpG/oligodeoxynucleotide stimulation)
- Deletion 17p, or presence of TP53 mutation
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
- PT/PTT/INR within 1.5 x the ULN
- Adequate renal function defined by serum creatinine less than 2 x ULN
- Adequate hepatic function:
- ALT/AST less than 2x ULN
- Tbili less than 1.5 X ULN unless bilirubin elevation is due to Gilbert's syndrome (total bilirubin <3)
- Subject must have adequate bone marrow function.
- Absolute neutrophil count ≥1.0 x103/μL
- Hemoglobin ≥ 11.0 g/dL
- Platelets ≥ 100 x 103/μL
Who cannot join
- Previous exposure to any systemic anti-cancer therapy as a treatment for CLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, or investigational therapy. Note, patients treated with chemotherapy for a prior non-hematologic malignancy if more than 5 years earlier are eligible.
- Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll.
- Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
- Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia purpura.
- Subject has prolymphocytic leukemia.
- Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
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- Subject requires warfarin or equivalent vitamin K antagonist
- Uncontrolled or active significant infection,
- History of or suspected or confirmed PML
- Clinically 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. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
- Patients with stroke or CNS hemorrhage within 6 months
- Pregnant or breastfeeding
- Women of childbearing potential (WCBP) who are sexually active with heterosexual partners must agree to use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib.
- Major surgical procedure within 28 days of first dose of study drug. If a subject had surgery, they must have recovered adequately from any toxicity or complications before the first dose of study drug.
- Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
- Subject is known to be positive for human immunodeficiency virus (HIV)
- Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR
- Active hepatitis B infection documented by a positive PCR for Hep B DNA. If hepatitis B serology is positive for hepatitis B core antibody, but Hep B DNA PCR is negative, patient is eligible to enroll.
- Subject requires strong CYP 3A4/5 inhibitors or inducers (Appendix B).
- Subject requires proton pump inhibitors. (Subjects that can transition to an H2 antagonist are allowed to enroll.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Early Intervention With Acalabrutinib in Patients With CLL at High Risk for Richter's Transformation
This study evaluates the effectiveness of acalabrutinib treatment in patients with chronic lymphocytic leukemia (CLL) deemed at high risk for Richter's Transformation (RT). This is a single arm study. Enrolled patients will initiate therapy with acalabrutinib and will dose continuously. While on study, subjects will be monitored monthly for the first 3 months, then every three months thereafter until disease progression, discontinuation due to toxicity, death, or study completion.
Read the detailed description
This is a multi-center, single arm, Phase II clinical trial to investigate the effectiveness of acalabrutinib treatment within 6 months of chronic lymphocytic leukemia (CLL) diagnosis for patients with CLL deemed at high risk for Richter's Transformation (RT).
- Conditions
- Chronic Lymphocytic Leukemia, CLL/SLL
- Being tested
- Acalabrutinib
- Keywords
- CLL, untreated
- Medical subject headings
- 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 CALQUENCE, ACP-196
Acalabrutinib, oral, 100 mg BID, continuous
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib | Experimental | Acalabrutinib 100 mg will be administered orally twice daily continuously in 28-day cycles until treatment is discontinued for any reason. Receives: Drug: Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration
Measured: 5 years
Secondary outcomes (7)
Event-free survival
Measured from time of study drug administration to time of progression, transformation to a more aggressive histology, treatment discontinuation due to toxicity, or death from any cause.
Measured: 5 years
Progression-free survival
Measured from time of study drug administration to progression or death, measured in months.
Measured: 5 years
Progression-free survival in patients with TP53 disruption
For subjects with TP53 disruption present at baseline, measured from time of study drug administration to progression or death, measured in months.
Measured: 5 years
Overall survival
Measured from time of study drug administration to death from any cause, measured in months.
Measured: 5 years
Percentage of subjects who do not develop Richter's Transformation within 2 years of study drug administration
Measured: 2 years
Median time to development of RT
Measured from time of study drug administration
Measured: 5 years
Safety of early interventional acalabrutinib in patients with chronic lymphocytic leukemia (CLL) at high risk for Richter's Transformation
Percentage of subjects who experience 1 or more adverse events.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study startMay 2022 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionJun 2026 (estimated)
Why it stopped: Company supplying drug/funding ceased support.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- John N Allan, M.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04660045
- Sponsor's protocol ID
- 20-11022876
- Status last verified
- Mar 2022
- First submitted
- 2 Dec 2020
- Last updated
- 5 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Early Intervention With Acalabrutinib in Patients With CLL at High Risk for Richter's Transformation
- ClinicalTrials.gov ID
- NCT04660045
- Acronym / sponsor ID
- 20-11022876
- Conditions
- Chronic Lymphocytic Leukemia, CLL/SLL
- Keywords
- CLL, untreated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Company supplying drug/funding ceased support.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2022 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 9 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effectiveness of acalabrutinib treatment in patients with chronic lymphocytic leukemia (CLL) deemed at high risk for Richter's Transformation (RT). This is a single arm study. Enrolled patients will initiate therapy with acalabrutinib and will dose continuously. While on study, subjects will be monitored monthly for the first 3 months, then every three months thereafter until disease progression, discontinuation due to toxicity, death, or study completion.
Detailed description
This is a multi-center, single arm, Phase II clinical trial to investigate the effectiveness of acalabrutinib treatment within 6 months of chronic lymphocytic leukemia (CLL) diagnosis for patients with CLL deemed at high risk for Richter's Transformation (RT).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib | Experimental | Drug: AcalabrutinibAcalabrutinib 100 mg will be administered orally twice daily continuously in 28-day cycles until treatment is discontinued for any reason. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
- The time from diagnosis to consent should be ≤6 months.
- Subject must be ≥ 18 years of age.
- Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
- Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL guidelines
Key exclusion criteria (20 listed)
- Previous exposure to any systemic anti-cancer therapy as a treatment for CLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, or investigational therapy. Note, patients treated with chemotherapy for a prior non-hematologic malignancy if more than 5 years earlier are eligible.
- Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll.
- Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
- Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia purpura.
- Subject has prolymphocytic leukemia.
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: CALQUENCE, ACP-196Acalabrutinib, oral, 100 mg BID, continuous | Drug | Acalabrutinib |
Primary outcome
Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration
Time frame: 5 years
7 secondary outcomes
Event-free survival
Time frame: 5 years
Progression-free survival
Time frame: 5 years
Progression-free survival in patients with TP53 disruption
Time frame: 5 years
Overall survival
Time frame: 5 years
Percentage of subjects who do not develop Richter's Transformation within 2 years of study drug administration
Time frame: 2 years
Median time to development of RT
Time frame: 5 years
Safety of early interventional acalabrutinib in patients with chronic lymphocytic leukemia (CLL) at high risk for Richter's Transformation
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
- WCM Joint Clinical Trials OfficeLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
John N Allan, M.D. principal investigator
Weill Medical College of Cornell University
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 Chronic Lymphocytic Leukemia and CLL/SLL, run by Weill Medical College of Cornell University 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 21 inclusion and 20 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: withdrawn, as of the sponsor's last update on 5 Apr 2022. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration (time frame: 5 years). 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 5 Apr 2022; AzTrials last refreshed its copy on 7 Nov 2026.