An Open-label, Phase 1b/2 Study of ACP-196 in Subjectswith Waldenström Macroglobulinemia

Phase 1

Conditions: Waldenström Macroglobulinemia
MedDRA version: 20.0Level: PTClassification code 10047804Term: Waldenstrom's macroglobulinaemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: 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-GB

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

Inclusion Criteria

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. 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.
7. This criterion was removed as of Protocol Amendment 7.
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 patientprivacy 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

Exclusion Criteria

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 acalabrutinib, 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 acalabrutinib.
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 proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
17. Absolute neutrophil count (ANC) < 0.75 x 10^9/L or platelet count <50 x 10^9/L. For subjects with disease involvement in the bone marrow, ANC < 0.50 x 10^9/L or platelet count < 30 x 10^9/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.