None listed
Conditions
Brief summary
This trial is for patients with primary mediastinal B-cell lymphoma (PMBL) and is evaluating if combining pembrolizumab with R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) will improve patient outcomes. All patients will receive the following treatment regimen: Cycle 1-2: R-pembro ‘window’ (21-day cycle) * rituximab 375mg/m2 Intravenous Infusion on Day 1 * pembrolizumab 200mg Intravenous Infusion on Day 1 Cycle 3-8: ‘Induction’ (21-day cycle) * rituximab 375mg/m2 Intravenous Infusion on Day 1 * cyclophosphamide 750mg/m2 Intravenous Infusion on Day 1 *doxorubicin 50mg/m2 Intravenous Infusion on Day 1 *vincristine 1.4mg/m2 Intravenous Infusion on Day 1 capped at 2mg *prednisolone 100mg oral tablet on Days 1-5 pembrolizumab 200mg Intravenous Infusion on D1 Cycle 9-17: Pembrolizumab ‘Consolidation’ (21-day cycle) * pembrolizumab 200mg Intravenous Infusion on Day1 Patients will have a PET/CT Scan at the following timepoints 1. After Registration 2. After the "Pembro" phase 3. After the "Induction" phase 4. Patients may have another PET/CT scan at the discretion of their treating physician. Patients will also have blood samples taken every three weeks whilst receiving treatment. It is hoped that this study may demonstrate that addition of pembrolizumab to R-CHOP may improve survival in patients with PMBL.
Interventions
The trial is a Phase II trial.
Patients will receive the following treatment
Cycle 1 and 2: R-pembro ‘window’ (21-day cycle)
* Rituximab 375mg/m2 Intravenous Infusion on Day 1
* Pembrolizumab 200mg Intravenous Infusion on Day 1
Cycle 3- to 8: ‘Induction’ (21-day cycle) -
* Rituximab 375mg/m2 Intravenous Infusion on Day 1
* Cyclophosphamide 750mg/m2 Intravenous Infusion on Day 1
* Doxorubicin 50mg/m2 Intravenous Infusion on Day 1
* Vincristine 1.4mg/m2 Intravenous Infusion on Day 1 capped
The trial is a Phase II trial. Patients will receive the following treatment Cycle 1 and 2: R-pembro ‘window’ (21-day cycle) * Rituximab 375mg/m2 Intravenous Infusion on Day 1 * Pembrolizumab 200mg Intravenous Infusion on Day 1 Cycle 3- to 8: ‘Induction’ (21-day cycle) - * Rituximab 375mg/m2 Intravenous Infusion on Day 1 * Cyclophosphamide 750mg/m2 Intravenous Infusion on Day 1 * Doxorubicin 50mg/m2 Intravenous Infusion on Day 1 * Vincristine 1.4mg/m2 Intravenous Infusion on Day 1 capped at 2mg * Prednisolone 100mg oral tablet on Day 1 to Day 5 * Pembrolizumab 200mg Intravenous Infusion on Day 1 Cycle 9-17: Pembrolizumab ‘Consolidation’ (21-day cycle) * Pembrolizumab 200mg Intravenous Infusion on D1 Upon completion of the cycle, the next cycle will commence.
Sponsors
Australasian Lymphoma and Leukaemia Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects aged equal to greater than 18 years at time of enrolment. 2. Able to give informed consent. 3. Clinical and histological diagnosis of PMBL, according to the current World Health Organization classification. 4. No previous treatment for lymphoma including chemotherapy, radiotherapy or other investigational drug. 5. Eastern Collaborative Oncology Group performance status 0-<=1. 6. Platelets >= 100x109/l; neutrophils >= 1.0x109/l at the time of study entry. 7. Creatinine clearance >=30ml/min (calculated according to MRDR or Cockcroft Gault equation) 8. Total bilirubin less than or equal to 1.5 × ULN, AST and ALT less or equal to 2..5 x ULN 9. LVEF greater or equal to 45%
Exclusion criteria
1. Known hypersensitivity to any study medication, including previous grade >=3 hypersensitivity reactions to monoclonal antibody therapy. 2. Active autoimmune disease; requiring immunosuppressive therapy within 6 months of study entry. 3. Other lymphoma subtypes, other than PMBL. 4. Central nervous system, meningeal or spinal cord involvement by lymphoma. 5. Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4). 6. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. – Please note that a short course of steroids (e.g. Oral Prednisolone 1mg/kg daily or equivalent for <=7 days duration) will be permitted if indicated for lymphoma symptoms (but should be avoided if possible)
Outcome results
None listed