Marginal Zone Lymphoma MedDRA version: 20.0 Level: PT Classification code 10076596 Term: Marginal zone lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK3475)
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Co
Sponsors
University Hospital Ulm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must have a proven pathological diagnosis of MZL, diagnosed by a reference pathology center. Patients must meet the following inclusion criteria to be eligible for participation in this study: Confirmed CD20 positive de novo or relapsed MALT Lymphoma in need of treatment following or being not eligible for local therapy (including surgery, radiotherapy and antibiotics e.g. for H. pylori-positive gastric lymphoma arisen at any extranodal site) OR Confirmed CD20 positive de novo or relapsed splenic MZL in need of treatment following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus) OR Confirmed CD20 positive de novo or relapsed nodal MZL in need of treatment following or not being eligible for local therapy (radiotherapy). The need of treatment is applicable in the case of B symptoms, deterioration of peripheral blood counts due to lymphoma infiltration of the bone marrow, rapid enlargement of lymph nodes or compression of vital organs by bulky disease. For nodal MZL and extragastric MALT lymphoma: At least one bi-dimensionally measurable lesion (= 1.5 cm in its largest dimension by CT/ PET-CT scan or MRI). Please refer to Appendix D. For splenic MZL (SMZL): In patients with splenic MZL, an enlarged spleen on CT scan and lymphoma cell infiltration has to be seen in bone marrow and/or peripheral blood. Please refer also to Appendix F. At least one of the following criteria must be fulfilled: Bulky progressive or painful splenomegaly one of the following symptomatic/progressive cytopenias: Hb 3 months Meet the following pretreatment laboratory criteria at the Screening visit conducted within 28 days of study enrollment (unless due to underlying lymphoma): Baseline platelet count = 75 x 109/L (if not due to BM infiltration by the lymphoma), absolute neutrophil count = 1.5 x 109/L. Hemoglobin = 9.0 g/dL or = 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks) International Normalized Ratio (INR) or Prothrombin Time (PT): = 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT): = 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT
Exclusion criteria
Exclusion criteria: ECOG performance status = 2 History of a malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for = 1 year prior to study enrolment visit, other malignancy treated with a curative intent and currently in complete remission, for = 3 years Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma Has had prior chemotherapy (systemic anti-cancer therapy), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or baseline value) from AEs due to a previously administered agent Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study Note: If a subject received major surgery, they must have recovered adequately from complications from the intervention prior to starting therapy Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of study enrolment visit Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension Treatment with any other investigational agent or participating in another clinical trial with an investigational product within 4 weeks prior to entering this study or within 5 x the half-life (t1/2) of the investigational product, whichever is longer Breastfeeding or Pregnancy Congestive heart failure > New York Heart Association (NYHA) class 2 Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) Myocardial infarction less than 6 months before start of study medication Uncontrolled arterial hypertension despite optimal medical management Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results Vaccination with a live vaccine within 30 days prior to start of therapy Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication Non-healing wound, ulcer, or bone fracture History or concurrent interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) Has received prior therapy 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 (e.g., CTLA-4, OX 40, CD137) Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this trial is to test the efficacy and toxicity of the treatment of Pembrolizumab/Rituximab in patients with MZL in need of treatment, who have failed or are not eligible for local therapy or relapsed after local or systemic therapy. For efficacy the rate of complete remissions (according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for non-gastric extranodal, nodal and splenic MZL) after therapy will be primarily analysed. For toxicity assessment treatment associated adverse events, quality of life and cumulative incidence of secondary malignancies will be documented. ;Secondary Objective: Response rate (CR, PR, CR or PR) Best response Time to best response Time to first response Progression free survival (PFS) Time to treatment failure (TTF) Duration of Response (DR) Cause specific survival (CSS) Overall survival (OS) Quality of life during therapy ;Primary end point(s): CR rate (CRR) after end of treatment (18 cycles);Timepoint(s) of evaluation of this end point: after 54 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response rate (CR, PR, CR or PR) Best response Time to best response Time to first response Progression free survival (PFS) Time to treatment failure (TTF) Duration of Response (DR) Cause specific survival (CSS) Overall survival (OS) Quality of life during therapy ;Timepoint(s) of evaluation of this end point: 54 - 58 weeks | — |
Countries
Austria, Germany
Contacts
Public ContactChristian Buske
University Hospital Ulm
Outcome results
None listed