Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: MabThera
Product Name: Rituximab
Product Code: [na]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Spon
Sponsors
LOXO ONCOLOGY INCORPORATED
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older per local regulations at time of enrollment. Type of Patient and Disease Characteristics 2. Confirmed diagnosis by redacted local laboratory report of CLL/SLL as defined by iwCLL 2018 criteria including the following: a) B-cells coexpressing the surface antigen CD5 together with at least one B-cell antigen (CD19, CD20, CD23) and either ¿ or ¿ light-chain restricted (for CLL/SLL patients). b) = 5 × 109 B lymphocytes/L (5000/µL) in the peripheral blood. (for CLL patients). c) Prolymphocytes may comprise = 55% of blood lymphocytes (for CLL patients). 3. A requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy such that at least 1 of the following should be met: a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (such as hemoglobin 13 cm). c) Massive nodes (i.e., = 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 =65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: 1. Known or suspected Richter's transformation to diffuse large B-cell ymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin lymphoma at any time preceding enrollment. 2. Presence of 17p deletion by fluorescence in-situ hybridization (FISH) (refer to Section 8.10.2) 3. Known or suspected history of central nervous system (CNS) involvement by CLL/SLL. 4. Active second malignancy. Patients with treated second malignancy who are in remission with life expectancy > 2 years and with documented Sponsor approval are eligible. Examples include: a) Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease. b) Adequately treated cervical carcinoma in situ without current evidence of disease. c) Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years and receiving adjuvant hormonal therapy. d) Localized prostate cancer undergoing active surveillance. e) History of treated and cured Hodgkin's disease or NHL within 5 years from diagnosis. 5. Major surgery, within 4 weeks of planned start of study treatment. 6. A significant history of renal, neurologic, psychiatric, endocrine,metabolic or immunologic, that, in the opinion of the Investigator, would adversely affect the patient's participation in this study or interpretation of study outcomes. 7. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) not on a stable regimen and dose for at least 4 weeks prior to study enrollment 8. Significant cardiovascular disease defined as any of the following: a) Unstable angina or acute coronary syndrome within the past 2 months, b) History of myocardial infarction within 3 months prior to planned start of study drug, c) Documented LVEF by any method of = 40% d) = Grade 3 NYHA functional classification system of heart failure, uncontrolled or symptomatic arrhythmias 9. Prolongation of the QT interval corrected (QTc) for heart rate using Fredericia's Formula (QTcF) > 470 msec on at least 2 of 3 consecutive ECGs, and mean QTcF > 470 msec on all 3 ECGs, during Screening. a) QTcF is calculated using Fredericia's Formula (QTcF = QT/(RR^0.33) b) Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities can be attempted at the Investigator's discretion, and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation or electrolyte supplementation. c) Correction of QTc for underlying bundle branch block (BBB) permissible. 10. Hepatitis B or hepatitis C testing indicating active/ongoing infection based on Screening laboratory tests as defined as: a) Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before randomization. Patients who are hepatitis B PCR positive will be excluded. b) Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded. c) For optional crossover, repeat testing is not required. 11. Active cytomegalovirus (CMV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate PFS of pirtobrutinib as monotherapy (Arm A) compared to BR (Arm B).;Secondary Objective: • To evaluate the effectiveness of Arm A compared to Arm B based on ORR and time to event(s) outcomes. • To evaluate the effectiveness of Arm A compared to Arm B based on patient reported outcomes.;Primary end point(s): Assessed by IRC: • PFS per iwCLL 2018 response criteria;Timepoint(s) of evaluation of this end point: The time from the date of randomization until PD or death from any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Assessed by Investigator: - PFS per iwCLL 2018 criteria - OS - TTNT, defined as time from the date of randomization to the date of the next systemic anticancer therapy for CLL/SLL (see Section 9 for full definition). • Assessed by Investigator and IRC: - ORR • DOR • Patient reported outcomes of: - TTW of CLL/SLL-related symptoms - TTW of physical functioning as measured by the physical function domain of the EORTC-QLQ-C30;Timepoint(s) of evaluation of this end point: PFS - the time from the date of randomization until PD (per iwCLL 2018 criteria, Section 10.6, Appendix 6) or death from any cause, whichever occurs first. ORR - the proportion of patients who achieve a BOR of CR, CRi, nPR, or PR at or before the initiation of subsequent anticancer therapy. OS is defined as the time from randomization until death from any cause. TTNT - the time from the date of randomization to the date of the initiation of the next systemic anticancer therapy for CLL/SLL or the first dose date of pirtobrutinib for Arm B patients who crossed over | — |
Countries
Australia, Austria, Belgium, Canada, China, Croatia, Czechia, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical and Scientific Services
IQVIA RDS GmbH
Outcome results
None listed