Trial Title:
A Single Arm Study of Acalabrutinib Conbimed With Obinutuzumab in Chinese Patients With Previously Untreated CLL
NCT ID:
NCT05950997
Condition:
Chronic Lymphocytic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Obinutuzumab
Acalabrutinib
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Acalabrutinib
Description:
100 mg capsules administered by mouth once daily (28-day cycles)
Arm group label:
previously untreated chronic lymphocytic leukemia.
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
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)
Arm group label:
previously untreated chronic lymphocytic leukemia.
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.
Detailed description:
Subject participation will include a Screening Phase, a Treatment Phase, a Follow-up
Phase.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men and women ≥18 years of age.
2. 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
3. Diagnosis of CD20+ CLL that meets published diagnostic criteria(Hallek 2018):
1. 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.
2. Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
3. Presence of ≥ 5 x 109 B lymphocytes/L (5000 μL) in the peripheral blood (at any
point since diagnosis).
4. Active disease meeting ≥ 1 of the following iwCLL 2018 criteria for requiring
treatment:
1. 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).
2. Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or
symptomatic splenomegaly.
3. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or
symptomatic lymphadenopathy.
4. 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.
5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to
corticosteroids.
6. 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.
5. Meet the following laboratory parameters:
1. 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.
2. 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.
3. Serum AST and ALT ≤3 x upper limit of normal (ULN).
4. Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert's syndrome
5. 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)
6. 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.
7. 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.
8. Men must agree to refrain from sperm donation during the study and for 90 days after
the last dose of Obinutuzumab, whichever is later.
9. Willing and able to participate in all required evaluations and procedures in this
study protocol, including swallowing capsules and tablets without difficulty.
10. 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).
Exclusion Criteria:
1. 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.
2. Any prior systemic treatment for CLL (note: Prior localized radiotherapy is
allowed).
3. Known CNS lymphoma or leukemia.
4. Known prolymphocytic leukemia or history of, or currently suspected, Richter's
syndrome.
5. 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).
6. 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.
7. 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.
8. History of prior malignancy that could affect compliance with the protocol or
interpretation of results, except for the following:
1. 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.
2. 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.
9. 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.
10. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
11. Received any investigational drug within 30 days or 5 half-lives (whichever is
shorter) before first dose of study drug.
12. 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.
13. Received a live virus vaccination within 28 days of first dose of study drug.
14. Known history of infection with HIV.
15. Any active significant infection (e.g., bacterial, viral or fungal, including
subjects with positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR]).
16. Serologic status reflecting active hepatitis B or C infection.
1. 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.
2. 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.
17. History of stroke or intracranial hemorrhage within 6 months before first dose of
study drug.
18. History of bleeding diathesis (e.g., hemophilia, von Willebrand disease).
19. Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists.
20. 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.
21. Breastfeeding or pregnant.
22. Concurrent participation in another therapeutic clinical trial.
23. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
24. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital
Address:
City:
Nanjin
Zip:
210029
Country:
China
Status:
Recruiting
Contact:
Last name:
Huayuan Zhu, PhD，MD
Phone:
86 25 68306034
Email:
huayuan.zhu@hotmail.com
Contact backup:
Last name:
Yeqin Sha, MD
Email:
yeqinsha@njmu.edu.cn
Start date:
April 16, 2024
Completion date:
September 30, 2026
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05950997
