Waldenström Macroglobulinemia
Conditions
Interventions
protocol treatment: 100 mg BID ACP-196
Sponsors
ACERTA PHARMA, BV
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: •Men and women >= 18 years of age. • 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. • 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: o Symptomatic hyperviscosity with an IgM >= 5,000 mg/dL o Disease-related neuropathy • 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). • Eastern Cooperative Oncology Group (ECOG) performance status of
Exclusion criteria
Exclusion criteria: • 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 480 msec. • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. • Any immunotherapy within 4 weeks of first dose of study drug. • 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). • Prior exposure to a BCR inhibitor (eg, BTK, phosphoinositide-3 kinase [PI3K], or spleen tyrosine kinase [SYK] inhibitors) or B-cell lymphoma 2 (BCL-2) inhibitor (eg, ABT-199). • 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 (= 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation. • Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection. • Major surgery within 4 weeks before first dose of study drug. • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. • History of a bleeding diathesis (eg, hemophilia, von Willebrand disease) • History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib. • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon) within 28 days of first dose of study drug. • Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) • Absolute neutrophil count (ANC) 2.5 x institutional upper limit of normal (ULN); total bilirubin > 2.5 x ULN; or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN. • Lactating or pregnant. • Concurrent participation in another therapeutic clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the ORR of acalabrutinib in subjects with WM as assessed by investigators. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives: • To determine the ORR of acalabrutinib by IRC • To determine the DOR of acalabrutinib by investigator and by IRC, respectively • To determine the progression-free survival (PFS) of acalabrutinib by investigator and by IRC, respectively • To determine the overall survival (OS) of acalabrutinib • To characterize the PK profile of acalabrutinib • To characterize the safety of acalabrutinib • To evaluate the effect of acalabrutinib in health-related quality of life Exploratory Objective: • To evaluate the PD effects of acalabrutinib | — |
Countries
Netherlands
Outcome results
None listed