A study of Zanubrutinib Compared with Ibrutinib in patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Conditions
- Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaMedDRA version: 21.1Level: LLTClassification code 10041152Term: Small lymphocytic lymphoma, consistent with CLL (Working Formulation)System Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001366-42-IT
- Lead Sponsor
- BeiGene Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1.Age 18 years or older
2.Confirmed diagnosis of CLL or SLL that meets the IWCLL criteria
3.CLL/SLL requiring treatment as defined by at least 1 of the following criteria:
a.Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
b.Massive (= 6 cm below left costal margin), progressive, or symptomatic splenomegaly
c.Massive nodes (= 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy
d.Progressive lymphocytosis with an increase of > 50% over a 2 month period or lymphocyte doubling time of < 6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of
absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30 x 10 9/L (30,000/µL), lymphocyte doubling
time should not be used as a single parameter to define treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (eg, infection) should be excluded.
e.Constitutional symptoms, defined as any 1 or more of the following disease-related symptoms or signs:
i.Unintentional weight loss of = 10% within the previous 6 months
ii Significant fatigue (ie, inability to work or perform usual activities)
iii.Fevers > 100.5ºF or 38ºC for = 2 weeks without other evidence of
infection
iv.Night sweats for > 1 month without evidence of infection
4.Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL. A line of therapy is defined as completing at least 2 cycles of treatment of standard regimen according to current NCCN or ESMO guidelines or of an investigational regimen on a clinical trial
5.Measurable disease by CT/magnetic resonance imaging (MRI). Measurable disease is defined as = 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular diametersor an extranodal
lesion must measure > 10 mm in longest perpendicular diameter (LPD).
6.Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2
7.Life expectancy = 6 months
8.Adequate bone marrow function as defined by:
a.Absolute neutrophil count (ANC) = 1000/mm3 (growth factor use is allowed), except for patients with bone marrow involvement in which case ANC must be = 750/mm3
- the screening hematology values confirming patient meets the ANC requirement must be dated at least 14 days following the most recent administration of pegfilgrastim and at least 7 days following the most recent administration of other myeloid growth factors (eg, G-CSF, GM-CSF)
b.Platelet = 75,000/mm3 (may be post-transfusion), except for patients with bone marrow involvement by CLL in which case the platelet count must be = 30,000/mm 3
c.Hemoglobin = 7.5 g/dL (may be post-transfusion)
9.Patient must have adequate organ function defined as:
a.Creatinine clearance = 30 mL/min (as estimated by the Cockcroft- Gault equation or the Modification of Diet in Renal Disease [MDRD] equation, or as measured by nuclear medicine scan or 24 hour urine
collection)
b.Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase = 2.5 × upper limit of normal unless due to CLL/SLL
c.Serum total bilirubin < 3.0 × upper limit of normal (unless documented Gilbert's syndrome)
10.Female patients of childbearing potential must practice highly effective methods (Section 5.1.2) of contraception initiated pri
FOR THE ENTIRE LIST PLEASE REFER TO PARAGRAPH 4.2 OF PROTOCOL
1. Known prolymphocytic leukemia or history of, or currently suspected, Richter’s transformation (biopsy based on clinical suspicion may be needed to rule out transformation)2. Clinically significant cardiovascular disease including the following: a. Myocardial infarction within 6 months before screening b. Unstable angina within 3 months before screening c. New York Heart Association class III or IV congestive heart failure (Appendix 4) d. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes) e. QTcF > 480 milliseconds based on Fridericia’s formula f. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place g. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg at screening 3. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, non-muscle-invasive or carcinoma in situ of the cervix or breast 4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 5. History of stroke or intracranial hemorrhage within 180 days before first dose of study drug 6. Severe or debilitating pulmonary disease 7. Unable to swallow study drug or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery
procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction 8. Active fungal, bacterial, and/or viral infection requiring systemic therapy 9. Known central nervous system involvement by leukemia or lymphoma 10. Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs 11. Known infection with HIV or serologic status reflecting active viral hepatitis B or C infection as follows: a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring for HBV reactivation b. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 12. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C 13. Major surgery within 4 weeks of the first dose of study drug 14. Prior treatment with a BTK inhibitor 15. Last dose of prior therapy for CLL/SLL = 14 days before randomization, with the following additional exclusion requirements: a. Treatment with monoclonal antibody-based therapy within 28 days of first dose of study drug b. Treatment with chimeric antigen receptor T-cell therapy within 180 days of first dose of study drug c. Treatment with Chinese herbal medicine with anticancer intent within 28 days of first dose of study drug d. Chemotherapy or radiation treatment within 21 days of first dose of study drug or hematopoietic stem cell transplantation within 90 days of first dose of study drug 16. Prior steroid use ¿ For prior corticosteroid use of 10
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