Chronic Lymphocytic LeukemiaNCT05950997
A Single Arm Study of Acalabrutinib Conbimed With Obinutuzumab in Chinese Patients With Previously Untreated CLL
A study testing Acalabrutinib and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This is a single-arm, prospective study to assess the efficacy and safety of acalabrutinib combined with obinutuzumab in subjects with previously untreated chronic lymphocytic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Acalabrutinib and Obinutuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteChina
- Study dates
- 16 Apr 2024to 30 Sep 2026
- Phase
- Interventional
- 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
- Men and women ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
- Diagnosis of CD20+ CLL that meets published diagnostic criteria(Hallek 2018):
- Monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.
- Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
- Presence of ≥ 5 x 109 B lymphocytes/L (5000 μL) in the peripheral blood (at any point since diagnosis).
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- Active disease meeting ≥ 1 of the following iwCLL 2018 criteria for requiring treatment:
- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL).
- Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
- Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
- Progressive lymphocytosis with an increase of > 50% over a 2-month period or (lymphocyte doubling time) LDT of < 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 x 109/L (30,000/μL) may require a longer observation period to determine the LDT. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids.
- Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:
- i Unintentional weight loss ≥ 10% within the previous 6 months before Screening.
- ii Significant fatigue (i.e., ECOG performance status 2; inability to work or perform usual activities).
- iii Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.
- iv Night sweats for > 1 month before Screening without evidence of infection.
- Meet the following laboratory parameters:
- ANC ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
- Platelet count ≥ 50,000 cells/μL (50 x 109/L), or ≥ 30,000 cells/μL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
- Serum AST and ALT ≤3 x upper limit of normal (ULN).
- Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert's syndrome
- Estimated creatinine clearance of ≥30 mL/min, calculated by Cockcroft-Gault (using actual body weight), or serum creatinine ≤2×ULN, (if male, [140-Age] x Mass [kg] / [72 x creatinine mg/dL]; multiply by 0.85 if female)
- Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib, or 18 months after the last dose of obinutuzumab, whichever is longer.
- Male subjects who are sexually active must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study and for 90 days after the last dose of Obinutuzumab, whichever is later.
- Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of Obinutuzumab, whichever is later.
- Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
Who cannot join
- Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
- Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
- Known CNS lymphoma or leukemia.
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
- Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).
- Corticosteroid use > 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or WBC count lowering are excluded.
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- Major surgery within 30 days before first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
- a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
- b. Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment.
- Significant cardiovascular disease such as 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 at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
- History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
- Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
- Received a live virus vaccination within 28 days of first dose of study drug.
- Known history of infection with HIV.
- Any active significant infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR]).
- Serologic status reflecting active hepatitis B or C infection.
- Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded.
- Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
- History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
- History of bleeding diathesis (e.g., hemophilia, von Willebrand disease).
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited.
- Breastfeeding or pregnant.
- Concurrent participation in another therapeutic clinical trial.
- Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital
Nanjin, Jiangsu, 210029
Huayuan Zhu, PhD，MD, 86 25 68306034, huayuan.zhu@hotmail.com
Yeqin Sha, MD, yeqinsha@njmu.edu.cn
About this study
Official title: A Single Arm Study of Acalabrutinib Combined With Obinutuzumab in Chinese Patients With Treatment-Naive Chronic Lymphocytic Leukemia
This is a single-arm, prospective study to assess the efficacy and safety of acalabrutinib combined with obinutuzumab in subjects with previously untreated chronic lymphocytic leukemia.
Read the detailed description
Subject participation will include a Screening Phase, a Treatment Phase, a Follow-up Phase.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Acalabrutinib, Obinutuzumab
- 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
100 mg capsules administered by mouth once daily (28-day cycles)
ObinutuzumabDrug
100 mg administered intravenously on Day 1 and 900 mg administered intravenously on Day 2, 1000 mg administered intravenously on Day 8 and 15 of cycle 2 and 1000 mg on Day 1 of subsequent cycles for a total of 6 cycles (28-day cycles)
| Study group | Role | What they receive |
|---|---|---|
| previously untreated chronic lymphocytic leukemia. | Experimental | Previously untreated CLL patients with ≥1 of the IWCLL 2018 criteria for requiring treatment will be enrolled. Treatment with acalabrutinib may be continued until treatment for 24 months, or until an unacceptable drug-related toxicity occurs or until disease progression, whichever occurs first. Dose modification provisions are provided in the study protocol. Treatment with obinutuzumab or obinutuzumab/chlorambucil is up to 6 cycles per the obinutuzumab package insert. Receives: Drug: Acalabrutinib; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival rate at 24 months
24-month progression-free survival rate is defined as the proportion of subjects without progression or death due to any cause at 24 months since the start of study drug. The evaluation of progression will be investigator-assessed per International Workshop on Chronic Lymphocytic Leukemia criteria(iwCLL2018) criteria.
Measured: At 24 months
Secondary outcomes (5)
Objective response rate (ORR)
ORR is defined as the proportionof subjects with complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission(nPR), or partial remission(PR) assessed by investigator per iwCLL2018 criteria.
Measured: 24 months after LPI
Duration of response (DOR)
DOR is defined as the time from the first documentation of objective response to the earlier time of disease progression (assessed by the investigator, per iwCLL 2018 criteria) or death from any cause. The same censoring rules and analysis methods will be applied as described for PFS.
Measured: At 24 months
24-month overall survival rate (24m OS rate)
24-month overall survival rate is defined as the proportion of subjects without death due to any cause at 24 months since the start of study drug.
Measured: At 24 months
Adverse Events (AEs)
AEs will be graded by the investigator according the NCI CTCAE v5.0 or higher for hematologic and nonhematologic AEs. Each AE verbatim term will be coded to a system organ class and a preferred term using the Medical Dictionary for Regulatory Activities (MedDRA).
Measured: Up to acalabrutinib treatment for 24 months
Treatment-Emergent Adverse Events
All treatment-emergent adverse events (TEAEs) will be summarized. In addition, AE incidence rates will also be summarized by severity and relationship to study drug.
Grade 3 or Grade 4 TEAEs; TEAEs leading to permanent study drug treatment discontinuation; TEAEs leading to dose reduction; serious TEAEs; and TEAEs resulting in death will be summarized.
Measured: Up to acalabrutinib treatment for 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2023
- Study start16 Apr 2024
- Primary completion31 May 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
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 The First Affiliated Hospital with Nanjing Medical 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 89 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Jianyong Li, PhD, MD, Principal investigator, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05950997
- Sponsor's protocol ID
- ESR-22-22033
- Status last verified
- May 2024
- First submitted
- 15 Jun 2023
- Last updated
- 9 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Study of Acalabrutinib Combined With Obinutuzumab in Chinese Patients With Treatment-Naive Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT05950997
- Acronym / sponsor ID
- ESR-22-22033
- Conditions
- Chronic Lymphocytic Leukemia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 89 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 16 Apr 2024 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 18 Jul 2023 (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 is a single-arm, prospective study to assess the efficacy and safety of acalabrutinib combined with obinutuzumab in subjects with previously untreated chronic lymphocytic leukemia.
Detailed description
Subject participation will include a Screening Phase, a Treatment Phase, a Follow-up Phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| previously untreated chronic lymphocytic leukemia. | Experimental | Drug: Acalabrutinib, Drug: ObinutuzumabPreviously untreated CLL patients with ≥1 of the IWCLL 2018 criteria for requiring treatment will be enrolled. Treatment with acalabrutinib may be continued until treatment for 24 months, or until an unacceptable drug-related toxicity occurs or until disease progression, whichever occurs first. Dose modification provisions are provided in the study protocol. Treatment with obinutuzumab or obinutuzumab/chlorambucil is up to 6 cycles per the obinutuzumab package insert. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Men and women ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
- Diagnosis of CD20+ CLL that meets published diagnostic criteria(Hallek 2018):
- Active disease meeting ≥ 1 of the following iwCLL 2018 criteria for requiring treatment:
- i Unintentional weight loss ≥ 10% within the previous 6 months before Screening.
Key exclusion criteria (28 listed)
- Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
- Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
- Known CNS lymphoma or leukemia.
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
- Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).
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 |
|---|---|---|
| Acalabrutinib100 mg capsules administered by mouth once daily (28-day cycles) | Drug | previously untreated chronic lymphocytic leukemia. |
| Obinutuzumab100 mg administered intravenously on Day 1 and 900 mg administered intravenously on Day 2, 1000 mg administered intravenously on Day 8 and 15 of cycle 2 and 1000 mg on Day 1 of subsequent cycles for a total of 6 cycles (28-day cycles) | Drug | previously untreated chronic lymphocytic leukemia. |
Primary outcome
Progression-free survival rate at 24 months
Time frame: At 24 months
24-month progression-free survival rate is defined as the proportion of subjects without progression or death due to any cause at 24 months since the start of study drug. The evaluation of progression will be investigator-assessed per International Workshop on Chronic Lymphocytic Leukemia criteria(iwCLL2018) criteria.
5 secondary outcomes
Objective response rate (ORR)
Time frame: 24 months after LPI
Duration of response (DOR)
Time frame: At 24 months
24-month overall survival rate (24m OS rate)
Time frame: At 24 months
Adverse Events (AEs)
Time frame: Up to acalabrutinib treatment for 24 months
Treatment-Emergent Adverse Events
Time frame: Up to acalabrutinib treatment for 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- 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.
Jianyong Li, PhD, MD principal investigator
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acalabrutinib and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
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 28 inclusion and 28 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: status not confirmed, as of the sponsor's last update on 9 May 2024. 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 China. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jianyong Li, PhD, MD (025-83718836, lijianyonglm@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival rate at 24 months (time frame: At 24 months). 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 9 May 2024.