Pembrolizumab in Combination With R-ICE Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma
NCT ID: NCT05221645
Last Updated: 2024-12-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE2
65 participants
INTERVENTIONAL
2022-06-27
2026-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
All patients will be randomised at study entry and will be stratified by relapse within 12 months or \> 12 months of first line therapy.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
All patients will be randomised at study entry and will be stratified by relapse within 12 months or \> 12 months of first line therapy.
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Control Arm A
Patients will receive three cycles of R-ICE. Each cycle is 21 days +/- 3 days Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2
All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol.
Rituximab
Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. Anti-CD20 mAbs, like rituximab, are classified by their CD20-binding characteristics, ability to induce complement-dependent cytotoxicity (CDC), and immune effector cell effects.
Ifosfamide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Carboplatin
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Etoposide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Experimental Arm B
Pembrolizumab 200mg Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2 Patients will receive up to 3 cycles of: P+R-ICE, where each cycle is 21 days long +/-\_3 days.
All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing P+R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol.
These patients will then be offered maintenance pembrolizumab every 3 weeks for one year.
Pembrolizumab
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1. Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment of patients across a number of indications because of its mechanism of action to bind the PD-1 receptor on the T cell.
Rituximab
Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. Anti-CD20 mAbs, like rituximab, are classified by their CD20-binding characteristics, ability to induce complement-dependent cytotoxicity (CDC), and immune effector cell effects.
Ifosfamide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Carboplatin
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Etoposide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pembrolizumab
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1. Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment of patients across a number of indications because of its mechanism of action to bind the PD-1 receptor on the T cell.
Rituximab
Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. Anti-CD20 mAbs, like rituximab, are classified by their CD20-binding characteristics, ability to induce complement-dependent cytotoxicity (CDC), and immune effector cell effects.
Ifosfamide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Carboplatin
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Etoposide
Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Refractory to, or relapsed following, first-line or second-line treatments with rituximab concurrently with anthracycline or anthracenedione-based chemotherapy or similar (etoposide allowed if comorbid).
Refractory disease must fulfil one of the following:
* Continuing partial response (PR) from termination of first-line treatment. It is strongly recommended the lymphoma be reconfirmed by biopsy however, if these procedures are deemed to be inappropriate, the CI may determine eligibility following review of the imaging results and disease history.
* Continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the lymphoma by biopsy (preferred) is recommended but not mandatory.
* Progressive disease (PD). Biopsy or reconfirmation of the lymphoma is recommended but not mandatory.
* Potentially eligible for high-dose therapy and peripheral blood progenitor cell rescue in the event of response
* Positive lesions shown on baseline PET-CT must be compatible with CT defined anatomical tumour sites.
* At least 2 demarcated lesions/nodes with a long axis \>1.5 cm and a short axis equal to 1.0cm or 1 clearly demarcated lesion/node with a long axis \>2.0cm and short axis of 1.0cm
* Previous therapy related toxicity should have resolved to a grade that the investigator deems appropriate to commence further treatment
* ECOG Performance Status 0 - 1
* Has provided written informed consent
* Willing to use acceptable contraception (see Section 4.6)
* Aged 18 or over
Exclusion Criteria
* Radiotherapy or cytotoxic drugs within two weeks of trial treatment
* Major surgery within 4 weeks of trial registration. If a subject had major surgery, more than 4 weeks ago, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
* Treatment with any unlicensed drug within 4 weeks of trial treatment
* History of stroke or intracranial haemorrhage within 6 months prior to registration
* Pre-existing peripheral neuropathy grade \>2
* Clinically significant cardiac disease (inc. unstable angina, acute myocardial infarction, congestive heart failure, a current LVEF of \<40%) within 6 months of registration
* Any significant uncontrolled medical condition or known hypersensitivity to the study drugs
* Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
* Other past or current malignancy within 2 years prior to registration unless in the opinion of the investigator it does not contraindicate participation in the study. Subjects who have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
* Known CNS involvement
* Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible.
Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible.
Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
* Screening laboratory values :
* platelets \<75x109/L (unless due to lymphoma involvement of the bone marrow)
* neutrophils \<1.0x109/L (unless due to lymphoma involvement of the bone marrow)
* creatinine \>2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance \>50mL/min)
* total bilirubin \>1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert's disease)
* ALT/AST \>2.5 times upper normal limit (unless due to lymphoma)
* alkaline phosphatase \>2.5 times upper normal limit (unless due to lymphoma)
* History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone will be eligible as will be patients with controlled Type I diabetes mellitus on a stable dose of insulin).
* Patients who have previously undergone allogeneic transplantation.
* Live vaccination within 28 days of study treatment.
* Pregnant or lactating females. Women of child-bearing potential should have negative pregnancy test.
* History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Known hypersensitivity to CHO cell products or any component of the pembrolizumab formulation.
* Previous treatment with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
* Corticosteroid use \>10 mg/day of prednisolone or equivalent, for purposes other than for lymphoma symptom control.
Patients receiving corticosteroid treatment with \<10 mg/day of prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisolone 100 mg or equivalent could be given for a maximum of 14 days as a pre-phase. A dose of up to 10mg or prednisolone or equivalent may be used during the screening phase to control symptoms.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Merck Sharp & Dohme LLC
INDUSTRY
University of Southampton
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Oxford Cancer & Haematology Centre, The Churchill Hospital
Headington, Oxford, United Kingdom
The Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
RHMCAN1402
Identifier Type: -
Identifier Source: org_study_id