A trial to see the effects of increased doses of ACP-196 (the test drug) in subjects with Leukemia or special types of Leukemia

• Conditions: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma (SLL), Richter's Syndrome or Prolymphocytic Leukemia; MedDRA version: 18.0Level: LLTClassification code 10073483Term: B-cell prolymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: LLTClassification code 10003910Term: B-cell small lymphocytic lymphoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10058728Term: Richter's syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000440-15-DE
• Lead Sponsor: Acerta Pharma BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03-23
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

•Men and women = 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, = 1 previous treatments for CLL/SLL.
•Must have measurable CLL/SLL defined as lymph nodes = 2 cm as measured in the longest diameter.
•Active disease meeting = 1 of the following IWCLL 2008 criteria for requiring treatment:
oEvidence 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).
oMassive (ie, = 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
oMassive nodes (ie, = 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
oProgressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (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), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
oAutoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
oConstitutional symptoms documented in the subject’s chart with supportive objective measures, as appropriate, defined as = 1 of the following disease-related symptoms or signs:
?Unintentional weight loss = 10% within the previous 6 months before Screening.
?Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.
?Night sweats for > 1 month before Screening without evidence of infection.
•ECOG performance status of = 2.
•Agreement to use 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 (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], true sexual abstinence [Please note that periodic abstinence, eg, calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception], or sterilized partner).
•Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
•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).
•Male subjects must agree to refrain from sperm donation during the study and for 30 days after the last dose of study drug.
•Treatment Naive only: Men and women = 18 years of age with confirmed diagnosis of CLL/SLL, who require treatment per National Cancer Institute (NCI) or International Working Group guidelines and a) do not want to receive chemoimmunotherapy or b) have comorbidities that would preclude chemoimmunotherapy.
•Ibrutinib Intolerant only: Men and women = 18 years of age with confirmed diagnosis of CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs.
•Richter’s Syndrome/Prolymphocytic Leukemia Transformation only: Men and women = 18 years of age and biopsy proven DLBCL Richter's transformation or prolymphocytic leukemia transform

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 < 2 years. Note: these cases must be discussed with the Medical Monitor.
•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.
•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%.
•Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
•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).
•Relapsed after, or refractory to, prior Btk inhibitor therapy (Note: Does not apply to Ibrutinib R/R Group).
•Any history of Richter's transformation (Note: Does not apply to Richter’s Syndrome or Ibrutinib R/R Groups).
•Concomitant use of medicines known to cause QT prolongation or Torsades de pointes (see Appendix 1).
•Central nervous system (CNS) involvement by lymphoma.
•Grade = 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.
•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).
•History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
•Requires treatment with a long-acting proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
•Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
•Major surgery within 4 weeks before first dose of study drug.
•ANC < 0.75 x 109/L or platelet count < 50 x 109/L unless there is bone marrow involvement.
•Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (total bilirubin = 2.5 x ULN allowed in subjects with autoimmune hemolytic anemia that is otherwise controlled); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 3.0 x ULN unless disease related.
•Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN.
•Significant screening ECG abnormalities including, 2nd degree AV block type II, 3rd degree block, atrial fibrillation, Grade 2 or higher bradycardia, and QTc = 480 ms.
•Cardiac troponin I levels above the limit of normal as specified by the manufacturer.
•Breast feeding or pregna

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified