An Open-label, Phase 1b/2 Study of ACP-196 in Subjectswith Waldenström Macroglobulinemia
- Conditions
- Waldenström MacroglobulinemiaMedDRA version: 18.0Level: PTClassification code 10047804Term: Waldenstrom's macroglobulinaemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.0Level: PTClassification code 10047805Term: Waldenstrom's macroglobulinaemia refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003212-36-ES
- Lead Sponsor
- Acerta Pharma BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 88
1. Men and women ? 18 years of age.
2. 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
3. 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
4. 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).
5. Eastern Cooperative Oncology Group (ECOG) performance status of ? 2.
6. Agreement to use acceptable methods of contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear or beget children.
7. Agreement to refrain from sperm donation during the study and for 30 days after the last dose of study drug.
8. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
9. 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 subject privacy regulations).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
1. 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.
2. 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 ACP-196, or put the study outcomes at undue risk.
3. 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.
4. 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.
5. Any immunotherapy within 4 weeks of first dose of study drug.
6. 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).
7. Prior exposure to a BCR inhibitor (eg, Btk, phosphoinositide-3 kinase [PI3K]]], or Syk inhibitors) or BCL-2 inhibitors (eg, ABT-199).
8. 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.
9. Grade ? 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.
10. 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.
11. Major surgery within 4 weeks before first dose of study drug.
12. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
13. History of a bleeding diathesis (eg, hemophilia, von Willebrand disease).
14. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
16. Requires treatment with long-acting proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
17. Absolute neutrophil count (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 x 109/L.
18. Creatinine > 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
19. Lactating or pregnant.
20. Concurrent participation in another therapeutic clinical trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of ACP-196 in subjects with previously treated WM as measured by standard response criteria.;Secondary Objective: ? To evaluate the preliminary efficacy of ACP-196 in subjects with previously untreated WM<br>? To characterize the PK profile of ACP-196 in both patient populations (treated and untreated WM)<br>? To evaluate the PD effects of ACP-196 in both patient populations (treated and untreated WM)<br>? To characterize the safety of ACP-196 in both patient populations (treated and untreated WM)<br>? To evaluate the effect of ACP-196 in health-related quality of life in both patient populations (treated and untreated WM);Primary end point(s): The primary endpoint of the study is the overall response rate, defined as a subject achieving a minor response or better according to the Response Assessment Criteria for WM as assessed by investigators.;Timepoint(s) of evaluation of this end point: after 30 days after stop study treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Efficacy:<br>? Duration of overall response <br>? Progression-free survival <br>? Overall survival <br><br>Safety:<br>? frequency, severity, and relatedness of adverse events (AEs)<br>? frequency of AEs requiring discontinuation of study drug or dose reductions<br>? effect of ACP-196 on peripheral T/B/NK cell counts<br>? effect of ACP-196 on serum immunoglobulin levels<br><br>Pharmacokinetics:<br>? plasma pharmacokinetics of ACP-196<br><br>Patient Reported Outcomes:<br>? health-related quality of life;Timepoint(s) of evaluation of this end point: after 30 days after stop study treatment