None listed
Conditions
Brief summary
The study is evaluating the efficacy and safety for dose reduced fludarabine, cyclophosphamide and intravenous obinutuzumab (G-FC3) versus oral chlorambucil and intravenous obinutuzumab (G-Clb) in previously untreated, comorbid, elderly patients with chronic lymphocytic leukaemia (CLL). Who is it for? You may be eligible to join this study if you are aged 65 years and older, have documented CD20+ B-cell CLL according to NCI/IWCLL criteria, previously untreated CLL requiring treatment according to NCI/IWCLL criteria, CIRS score >= 6, an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 at screening, able to comply with study protocol procedures and a minimum of 14 months of follow-up, and a life expectancy of at least 6 months. Trial details Participants in this study will be randomly (by chance) divided into one of two groups. Participants in one group will receive obinutuzumab (GA101) combined with fludarabine and cyclophosphamide (G-FC3). GA101 will be administered intravenously, 100 mg day 1 cycle 1, 900 mg day 2 cycle 1, 1000 mg day 8 and 15 cycle 1, 1000 mg day 1 cycles 2-6. Fludarabine will be administered orally, 24mg/m2 day 1-3 cycles 1-6. Cyclophosphamide will be administered orally, 150mg/m2 days 1-3 cycle 1-6. Participants in the second study group will receive GA101 with chlorambucil (G-Clb). GA101 will be administered intravenously, 100 mg day 1 cycle 1, 900 mg day 2 cycle 1, 1000 mg day 8 and 15 cycle 1, 1000 mg day 1 cycles 2-6. Chlorambucil will be administered orally, 150mg/m2 days 1-3 cycle 1-6. A treatment cycle is 28 days in length. A maximum of 6 cycles of therapy will be administered to each patient.
Interventions
The intervention includes; ARM 1 obinutuzumab combined with fludarabine and cyclophosphamide (G-FC3). A treatment cycle is 28 days in length. A maximum of 6 cycles of therapy will be administered to each patient. GA101 (intravenous) 100 mg day 1 cycle 1, 900 mg day 2 cycle 1, 1000 mg day 8 and 15 cycle 1, 1000 mg day 1 cycles 2-6. Fludarabine (oral), 24mg/m2 day 1-3 cycles 1-6. Cyclophosphamide (oral) 150mg/m2 days 1-3 cycle 1-6.
Sponsors
Australasian leukemia and lymphoma group (ALLG)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Documented CD20+ B-cell CLL according to NCI/IWCLL criteria (Hallek et al. 2008) Previously untreated CLL requiring treatment according to NCI/IWCLL criteria (Hallek et al. 2008). CIRS score >= 6 Age >= 65 years old An ECOG performance status score of 0-2 at Screening Able to comply with study protocol procedures and a minimum of 14 months of follow-up Has provided written informed consent Life expectancy at least 6 months Haematological parameters at Screening as defined by: a. ANC (segs + bands) >1.5 x 10^9/L unless related to CLL b. Platelet count >50 x 10^9/L Calculated creatinine clearance >= 40ml/min at Screening (Cockcroft-Gault formula) In men who are not surgically sterile, must agree to use a barrier method of contraception for >= 3 months after the last obinutuzumab dose. In addition, male participants must agree to request that their female partners of childbearing potential use an additional method of contraception.
Exclusion criteria
Patients who have received previous CLL treatment Transformation of CLL to aggressive NHL (Richter’s transformation) Prior treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1, unless administered for indications other than CLL at a dose equivalent to less than or equal to 30 mg/day prednisolone Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying leukemia): a. AST or ALT > 2.5 × ULN b. Total bilirubin greater than or equal to 3 × ULN One or more individual organ / system impairment score(s) of 4 as assessed by the CIRS definition, excluding the Eyes, Ears, Nose, Throat and Larynx organ system Prior diagnosis of malignancy, unless: a. the malignancy has been treated with a curative intent and there is no evidence of recurrence or b. in remission without treatment for greater than or equal to 2 years prior to study enrolment Previous adverse reaction to any of the trial drug/s Previous severe allergic or anaphylactic reaction to monoclonal antibody therapy Vaccination with live vaccines within 28 days prior to start of treatment Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis Participation in other therapeutic studies in the last 28 days except for studies with a non-medical intervention. Documented evidence of receiving placebo will be required. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm) Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalisation (relating to the completion of the course of antibiotics, except if for tumour fever) within 4 weeks prior to the start of Cycle 1 Positive test results for hepatitis C infection: a. Positive Hepatitis C virus [HCV] antibody serology testing. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA Hepatitis B infection defined as positive hepatitis B virus surface antigen (HBsAg) serology or hepatitis B core antibody (HBcAb). Known history of human immunodeficiency virus (HIV) seropositive status Positive test results for human T-lymphotropic virus 1 (HTLV 1): a. HTLV testing is required in participants from endemic countries (Japan, countries in the Caribbean basin, South America, Central America, sub Saharan Africa, and Melanesia) Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Outcome results
None listed