Relapsed or refractory diffuse large B-cell lymphoma. MedDRA version: 14.1 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Revlimid
Product Name: Lendalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lenalidomide
CAS Number: 191732-72-6
Current Sponsor code: CC-5013
Other descriptive name: CDC
Sponsors
The Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven CD20+ Diffuse Large B-Cell Lymphoma (DLBCL) 2. Availability of a tumour block containing adequate histological material for central pathology review and establishment of morphological and ontogenic subtype. Surgically acquired tissue samples are preferred but if core biopsy is the only suitable means by which to acquire a tissue sample then it is suggested than at least 2 cores are taken so that one can be embedded and sent for central review and one retained locally. 3. Relapsed after or refractory to one prior line of chemotherapy for DLBCL containing both rituximab and an anthracycline (eg R-CHOP) o ‘Relapsed’ is defined as investigator assessed progression after first line treatment o ‘Refractory’ is defined as patients who progressed during or who did not achieve complete remission with first line treatment (which should include radiotherapy if the patient had localised refractory disease) 4. Eligible for combination chemotherapy regimen 5. Patient is =18 years of age on the day of signing informed consent. 6. ECOG performance status 0, 1 or 2. 7. Baseline PET/CT scans must demonstrate FDG avid disease compatible with CT defined anatomical tumour sites. 8. Adequate bone marrow function: absolute neutrophil count (ANC) =1.0x109/l; white blood cell count = 3x109/l; platelets = 100x109/l; haemoglobin (Hb) = 9g/dl (can be post-transfusion), unless deemed disease related 9. Adequate renal function: calculated creatinine clearance =40ml/minute. 10. Adequate liver function: serum bilirubin =1.5x ULN; ALT/AST =2.5x ULN; ALP =3x ULN (in the absence of liver metastases). If liver metastases are present, ALT, AST or ALP =5x ULN are permitted. Isolated hyperbilirubinaemia due to Gilbert’s disease is acceptable 11. Female patient of childbearing potential (FCBP) must have two negative serum ß-hCG pregnancy tests at baseline. 12. FCBP agreeable to practice sexual abstinence or use two forms of contraception from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs. 13. Male patients agreeable to practice sexual abstinence use condoms from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs. 14. Recovery from toxicity from previous anti-cancer treatment to = grade 1 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 56 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Documented or symptomatic central nervous system involvement or leptomeningeal disease. 2. Any other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial, including active or chronic infection, poorly controlled diabetes mellitus, congestive cardiac failure, cardiac arrhythmia, coronary artery disease, cerebrovascular disease, or severe pulmonary disease 3. Any other malignancies diagnosed or treated within the last 5 years (other than curatively treated basal cell or squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix or breast). 4. Received drug treatment for cancer within 21 days of commencing study treatment. 5. Received previous lenalidomide 6. Evidence of human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or active hepatitis B infection. 7. Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing study treatment. 8. Hypersensitivity or contraindication to any of the study drugs as stated in the SmPCs for each of the study drugs. 9. Prior stem cell or solid organ transplant 10. Treatment with an investigational product within 30 days prior to enrolment 11. Not able to provide fully informed consent because of intellectual impairment or psychiatric disorder 12. Patient unwilling or not able to adhere to the Lenalidomide Pregnancy Prevention Programme (Appendix I)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the complete response rate (rate of patients put into remission) of treatment with LR-GEM (lenalidomide, rituximab, gemcitabine and methylprednisolone) and R-GEM-P (rituximab, gemcitabine, cisplatin and methylprednisolone) following 3 cycles of induction treatment as second-line therapy for patients with diffuse large B-cell lymphoma (DLBCL)(a common type of aggressive lymphoma in adults).;Secondary Objective: To assess, in both arms: • Overall response rate following 3 cycles of induction treatment • Event-free survival • Overall survival • Rate of successful stem cell harvest • Toxicity • Subgroup analyses will be performed to assess whether variation in the following factors causes a difference in the primary endpoint result: cell-of-origin immunohistochemical subtype using the Choi classification method(GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), International Prognostic Index (IPI)((0-2 vs 3 or more), time to relapse from previous treatment ( 12 months), and eligibility for ASCT at randomisation ;Timepoint(s) of evaluation of this end point: The primary outcome measure will be evaluated after 3 cycles of induction treatment.;Primary end point(s): To assess the complete response rate after 3 cycles of induction treatment to R-GEM-P and LR-GEM. Complete response rate is assessed using the Modified IWG Revised Response Criteria for Malignant Lymphoma 2007, based on central review by the trial radiologists, and incorporating bone marrow aspirate and trephine results. Assessment will be done in a blinded fashion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare, between both arms: • Overall response rate following 3 cycles of induction treatment evaluated by IWG 2007 criteria (Cheson JCO 2007) • Event-free survival • Overall survival • Rate of successful stem cell harvest • Toxicity • Subgroup analyses will be performed on the primary endpoint by cell-of-origin immunohistochemical subtype using the Choi method(GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), IPI (0-1 vs ?2), and previous response to treatment (?12 vs > 12 months), and eligibility for ASCT at randomisation ;Timepoint(s) of evaluation of this end point: Overall response rate will be evaluated after 3 cycles of induction treatment. rate of successful stem cell harvest will be evaluated after 3 cycles of induction treatment plus 2 weeks. Subgroup analyses and toxicity can be evaluated after 3 cycles of induction treatment. Overall survival, event-free survival and toxicity will be evaluated once all patients have a minimum of 2 years on study, and again at the end of the study. | — |
Countries
United Kingdom
Contacts
Public ContactMs Bijal Patel
Royal Marsden NHS Foundation Trust
Outcome results
None listed