Acalabrutinib for Waldenström Macroglobulinemia

Inclusion criteria

• {"criterion_text":"- Men and women ≥ 18 years of age.\n- Previously treated cohort only: A confirmed diagnosis of WM, which has relapsed after, or been refractory to ≥ 1 prior therapy for WM and which requires treatment\n- Previously untreated cohort only: A confirmed diagnosis of previously untreated WM in subjects who require treatment and do not want to receive chemoimmunotherapy or have comorbidities that would preclude chemoimmunotherapy such as: •Symptomatic hyperviscosity with an IgM ≥ 5,000 mg/dL •Disease-related neuropathy\n- Serum concentration of IgM, as measured by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE), that exceeds the upper limits of normal or measurable nodal WM (defined as the presence of ≥1 lymph node that measures ≥ 2.0 cm in the longest diameter and ≥ 1.0 cm in the longest perpendicular diameter).\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n- Women who are sexually active and can bear children must agree to use highly effective forms of contraception during the study and for 2 days after the last dose of acalabrutinib. Highly effective forms of contraception are defined in the protocol.\n- This criterion was removed as of Protocol Amendment 7.\n- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules or tablets without difficulty.\n- 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

• {"criterion_text":"- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years. Note: These cases must be discussed with the Medical Monitor.\n- A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.\n- Known history of HIV or active infection with HCV or hepatitis B virus (HBV) or any uncontrolled active systemic infection.\n- Major surgery within 4 weeks before first dose of study drug.\n- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.\n- History of a bleeding diathesis (eg, hemophilia, von Willebrand disease).\n- History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.\n- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.\n- Requires treatment with PPIs (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: this criterion no longer applies to patients who have switched from acalabrutinib capsules to tablets\n- ANC <0.75 x 109/L or platelet count <50 x 109/L. For subjects with disease involvement in the bone marrow, ANC <0.50 x 109/L or platelet count <30 x109/L.\n- Creatinine >2.5 x institutional ULN; total bilirubin >2.5 x ULN; or AST or ALT >3.0 x ULN.\n- Lactating or pregnant.\n- Concurrent participation in another therapeutic clinical trial.\n- 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%, or QTc > 480 msec.\n- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.\n- Any immunotherapy within 4 weeks of first dose of study drug.\n- For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).\n- Prior exposure to a BCR inhibitor (eg, Btk, phosphoinositide-3 kinase [PI3K], or Syk inhibitors) or BCL-2 inhibitors (eg, ABT-199).\n- Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of WM or other conditions. Note: Subjects may use topical or inhaled corticosteroids or low-dose steroids (≤ 10 mg of prednisone or equivalent per day) as therapy for comorbid conditions. During study participation, subjects may also receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions.\n- Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation."}

Primary endpoints

• {"endpoint_text":"- ORR, defined as a subject achieving a MR or better according to the response assessment criteria for WM as assessed by the investigator","definition_or_measurement_approach":"Defined as a subject achieving a MR or better according to the response assessment criteria for WM as assessed by the investigator."}
• {"endpoint_text":"- ORR, defined as a subject achieving a MR or better according to the response assessment criteria defined by modified 3rd IWWM workshop criteria as assessed by the investigator","definition_or_measurement_approach":"Defined as a subject achieving a MR or better according to the response assessment criteria defined by modified 3rd IWWM workshop criteria as assessed by the investigator."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: •DOR assessed by the investigator using response assessment criteria for WM and modified 3rd IWWM workshop criteria •\tPFS assessed by the investigator using response assessment criteria for WM and Modified 3rd IWWM workshop criteria •\tOverall survival (OS) •Effect of acalabrutinib on peripheral T/B/NK cell counts •Effect of acalabrutinib on serum immunoglobulin levels","definition_or_measurement_approach":"DOR and PFS assessed by the investigator using response assessment criteria for WM and modified 3rd IWWM workshop criteria; OS measured as overall survival; immunologic effects measured by peripheral T/B/NK cell counts and serum immunoglobulin levels."}
• {"endpoint_text":"- Safety: •Frequency, severity, and relatedness of AEs •Frequency of AEs requiring discontinuation of study drug or dose reductions","definition_or_measurement_approach":"Safety assessed by frequency, severity and relatedness of adverse events and frequency of AEs leading to discontinuation or dose reduction."}
• {"endpoint_text":"- Pharmacokinetics: •Plasma pharmacokinetics of acalabrutinib","definition_or_measurement_approach":"Plasma pharmacokinetic profiling of acalabrutinib."}
• {"endpoint_text":"- Patient Reported Outcomes (PRO): •Health-related quality of life","definition_or_measurement_approach":"Health-related quality of life measured via patient-reported outcome instruments (as specified in protocol)."}

France

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

22-09-2025

Processing Time Days

454

Number Of Sites

2

Number Of Participants

2

Greece

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

25-09-2025

Processing Time Days

457

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

456

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Acerta Pharma B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

IQVIA RDS Hellas Single Member S.A.

Responsibilities

sponsorDuties codes: 1,12

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1,12

Third parties

• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"sponsorDuties codes: 1,12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Astrazeneca Pharmaceuticals LP","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,12","organisation_type":"Pharmaceutical company"}