Phase 2 study of ibrutinib plus venetoclax treatment for patients suffering from chronic lymphocytic leukemia / small lymphocytic lymphoma who have never received treatment for this condition previously.
- Conditions
- Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)MedDRA version: 19.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864MedDRA version: 19.0Level: HLTClassification code 10003909Term: B-cell small lymphocytic lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002293-12-ES
- Lead Sponsor
- Pharmacyclics LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
2. Active disease meeting at least 1 of the following IWCLL criteria for requiring treatment:
- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
-Massive, progressive, or symptomatic splenomegaly
-Massive nodes or progressive or symptomatic lymphadenopathy
-Progressive lymphocytosis
-Constitutional symptoms
3. Measurable nodal disease by computed tomography (CT).
4. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to screening defined as:
- Absolute neutrophil count (ANC) >750 cells/µL (750 cells/mm3 or 0.75 x 109/L)
- Platelet count >30,000/µL (30,000 cells/mm3 or 30 x 109/L)
- Hemoglobin >8.0 g/dL
5. Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) =3.0 x upper limit of normal (ULN)
-Estimated Creatinine Clearance (CrCl) =60 mL/min (Cockcroft- Gault)
- Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)
6. Prothrombin time (PT)/International normal ratio (INR) <1.5 x (upper limit of notmal) ULN and PTT (activated partial thromboplastin time [aPTT]) <1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder).
7. Men and women =18 and <70 years of age.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for =1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of reproductive potential must have a negative serum pregnancy test upon study entry.
10. Male and female subjects of reproductive potential who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence2, or sterilized partner) and a barrier method (eg, condom, cervical ring, sponge, etc) during the period of therapy and for 30 days for females and 90 days for males after the last dose of study drug. Male subjects must agree to refrain from sperm donation until 90 days after the last dose of study drug.
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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
1. Any prior therapy (including but not limited to chemotherapy, targeted therapy, immunomodulating therapy, radiotherapy, and/or monoclonal antibody) used for treatment of CLL or SLL.
2. History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for =3 before the first dose of study drug and felt to be at low risk for recurrence by the treating physician
-Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
3. Known or suspected history of Richter’s transformation.
4. Concurrent administration of >20 mg/day of prednisone within 7 days of initiation of study drug unless indicated for prophylaxis or management of allergic reactions (eg, contrast).
5. Known hypersensitivity to one or more study drugs.
6. Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for TLS.
7. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
8. Recent infection requiring systemic treatment that is ongoing or was completed =14 days before the first dose of study drug, or any uncontrolled active systemic infection.
9. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia).
10. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
11. Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
12. Major surgery within 4 weeks of first dose of study drug.
13. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk.
14. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment.
15. Unable to swallow capsules/tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
16. Concomitant use of warfarin or other vitamin K antagonists.
17. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
18. Currently active, clinically significant hepatic impairment Child-Pugh Class B or C according to the Child Pugh classification.
19. Lactating or pregnant.
20. Unwilling or unable to participate in all required study evaluations and procedures.
21. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method