Chronic Lymphocytic Leukaemia (CLL). MedDRA version: 17.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: Obinutuzumab
Product Code: GA-101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Concentration
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • At least 18 years old • Previous confirmation of B-CLL with a characteristic immunophenotype (for example, CD5+, CD19+, CD23+ lymphoproliferative disorder) on peripheral blood flow cytometry • Maximum of three prior therapies received for CLL treatment and between 3 and 24 months post therapy at registration. • Response to most recent chemotherapy treatment for CLL with PR, CRi or CR • World Health Organisation (WHO) performance status (PS) of 0 or 1 • Able to provide written informed consent • Peripheral B-Cell count =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: • Disease progression after response to latest therapy • Active infection • Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies • Previous treatment with obinutuzumab • CNS involvement with CLL • Mantle cell lymphoma • Moderate or severe cardiac disease that would preclude treatment with obinutuzumab • Other severe, concurrent diseases or mental disorders that could interfere with ability to participate • Known HIV positivity • Active secondary malignancy excluding basal cell carcinoma • Active haemolysis • Patients previously treated with allogeneic Stem Cell Transplant • Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished • Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished, unless they are surgically sterile • Persisting severe pancytopenia (neutrophils <0.5 x 10^9/L or platelets <50 x 10^9/L) or trans fusion dependent anaemia • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. • Positive serology for Hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question this trial aims to answer is does obinutuzumab given within 3-12 months following a good response to prior treatment for chronic lymphocytic leukaemia (CLL) improve the length of time that patients are progression free when compared to having no consolidation treatment. The phase II primary objective is to determine the rate of achieving MRD negativity and to assess the safety of obinutuzumab in a consolidation setting. The phase III primary objective is to compare consolidation therapy with obinutuzumab against no consolidation therapy with respect to progression-free survival in participants who responded to previous therapy with a complete or good partial remission with low levels of MRD.;Secondary Objective: To assess and compare between trial arms: • Proportion of participants with undetectable minimal residual disease (MRD) (as defined by the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) criteria) • Overall survival • Treatment-free survival • Response and rate of response to therapy (as defined by IWCLL criteria) • Progression-free survival and overall survival for participants who are or become MRD negative • Duration of MRD negativity for participants who become MRD negative • Safety and toxicity • Health related quality of life ;Primary end point(s): Phase II - Proportion of participants with undetectable minimal residual disease at 6 months post randomisation. Phase III - Progression free survival: time from randomisation to first documented evidence of disease progression (as defined by IWCLL criteria) or death from any cause. Participants who do not progress will be censored at the last date they were known to be alive and progression free. ;Timepoint(s) of evaluation of this end point: Analysis on the phase II primary endpoint, proportion of participants with undetectable minimal residual disease, will be carried out after 9 and 23 participants have received at least 4 weeks of ob | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary endpoints will be analysed when at least 120 participants have progressed and there is sufficient follow up of participants, anticipated to be 3 years after the close of recruitment, but survival analyses will also be updated at a later as more data becomes available.;Secondary end point(s): Proportion of participants with undetectable MRD assessed at 6 months post randomisation in the obinutuzumab arm will be summarised with 95% confidence intervals reported. Overall survival (OS): Cox proportional hazards model will be fitted to analyse time from randomisation until death, adjusting for the minimisation factors. Overall survival curves will be reported by trial arm using Kaplan-Meier methods, and hazard ratios and corresponding 95% confidence intervals will be calculated. Treatment-free survival (TFS): Cox proportional hazards model will be fitted to analyse time from randomisation until next treatment or death, adjusting for the minimisation factors. Treatment-free survival curves will be reported by trial arm using Kaplan-Meier methods, and hazard ratios and corresponding 95% confidence intervals will be calculated. Response will be assessed at 6 months post randomisation in the obinutuzumab arm, as defined by IWCLL criteria. Response categories and changes in response from previous therapy will be summarised. The proportion of participants achieving a Complete Response (CR+CRi) and an Overall Response (at least a PR) will be summarised with corresponding 95% confidence intervals. Progression-free survival and overall survival from date of first documentation of MRD eradication: the analyses to compare PFS and OS for participants who are MRD negative at registration with those who become MRD negative after obinutuzumab consolidation will be the same as those for the randomised treatment groups, with the exception that survival will be calculated from the end date of prior treatment for CLL. Duration | — |
Countries
United Kingdom
Contacts
Public ContactJamie Oughton
UNITED KINGDOM
Outcome results
None listed