Previously untreated, high tumour burden follicular lymphoma MedDRA version: 21.1 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Rituximab (for intravenous infusion)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must be =18 years of age at the time of signing the informed consent form. 2. Must be able to adhere to the study visit schedule and other protocol requirements. 3. Must have a documented diagnosis of follicular lymphoma (grade 1, 2 or 3a). 4. Must be at non-contiguous stage II, stage III or stage IV. 5. Must fulfil at least one of the Groupe d'Etude des Lymphomas Folliculaires (GELF) GELF criteria for high tumour burden: a. Systemic symptoms (> 10% weight loss, temperature = 38°C for more than 5 days, abundant night sweats) b. Performance status (PS) greater than 1 according to the Eastern Cooperative Oncology Group (ECOG) scale c. Elevated lactate dehydrogenase (LDH) level d. ß2-microglobulin level greater than 25.5 nM/L (3 µg/mL) e. A single lymph node larger than 7 cm f. Involvement of at least 3 nodal sites, each with diameter greater than 3 cm g. Marked splenomegaly h. Organ failure i. Pleural effusion or ascites j. Orbital or epidural involvement k. Blood infiltration l. Cytopenia 6. Must not have received prior systemic therapy (local radiotherapy is permitted). 7. Must have a WHO performance status score of less than or equal to 2. 8. Must agree to adhere to the Celgene guidance on pregnancy prevention. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 340
Exclusion criteria
Exclusion criteria: 1. Any serious medical condition that would prevent the subject from participating in the study. 2. Known active infection with HIV, HBV or HCV. 3. Pregnant or lactating females. 4. Central nervous system involvement as documented by spinal fluid cytology or imaging. 5. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer (TNM stage of T1a or T1b) 6. Any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) 3.0 x upper limit of normal (ULN) d. Serum total bilirubin >1.5 x ULN unless due to Gilbert's Syndrome or biliary obstruction by lymphoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To confirm that leaving out rituximab maintenance in good-risk (PET -ve) patients does not lead to earlier relapses but reduces side effects and complications such as infection. 2. To see whether adding lenalidomide to rituximab maintenance in PET +ve patients prolongs remissions and improves life span. ;Secondary Objective: a) To see if adding lenalidomide to rituximab maintenance in PET +ve patients patients can make the PET scans return to normal. b) To understand the impact of the different treatments on quality of life. c) To understand the psychological impact of the different treatments. d) To understand the reasons why patients choose to participate or not participate in the study. e) To understand how much each of the treatments costs the NHS. f) To find new markers that can predict how well treatment is likely to work.;Primary end point(s): The primary outcome is progression-free survival (PFS). This is the time from randomisation until progression or death from any cause.;Timepoint(s) of evaluation of this end point: Patients will be assessed for disease progression by physical examination at the end of the induction phase of treatment and at every subsequent study visit. These visits occur every 4 weeks during the 2-year maintenance phase in the PET +ve group, every 8 weeks during the maintenance phase in the PET -ve group and every 24 weeks thereafter. Additional assessments will be performed between planned study visits if there is any suspicion of disease progression. In addition, CT scans will be performed at the end of the induction phase, at the end of the maintenance phase and every year thereafter until disease progression. An additional scan will be performed in the PET +ve group after 1 year of the maintenance phase as these patients are at risk of earlier progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Anatomical response to induction therapy b) Metabolic response to induction therapy c) Conversion to PET negativity (PET +ve group only) d) Overall survival e) Time to next treatment f) Time to next chemotherapy g) Toxicity h) Quality of life i) Psychological assessment j) Cost-effectiveness ;Timepoint(s) of evaluation of this end point: Anatomical response to induction therapy will be based on a pre- and post-induction CT scan and bone marrow biopsy. Metabolic response to induction therapy will be based on a pre- and post-induction PET CT scan. Conversion from PET positivity to PET negativity in the PET +ve group will be based on a PET-CT scan performed 1 year into the maintenance phase. Overall survival will be assessed continuously. Time to next treatment and next chemotherapy will be captured via follow-up assessments. Toxicity will be assessed at each study visit, while quality of life and psychological assessments will be performed post-induction, before each cycle of maintenance, and every 24 weeks thereafter until disease progression. Cost effectiveness will be calculated from multiple endpoints already described. | — |
Countries
United Kingdom
Contacts
Public ContactCRUK Liverpool Cancer Trials Unit
University of Liverpool
Outcome results
None listed