Efficacy of pembrolizumab in patients with marginal zone lymphoma

Phase 1

• Conditions: Marginal Zone Lymphoma; MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000187-28-DE
• Lead Sponsor: niversity Hospital Ulm

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-08-04
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 56

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 < 10 g/dL, or Platelet count < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration)
splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites if not being eligible for local therapy
SMZL with concomitant hepatitis C infection which has not responded to or are relapsed after Interferon and/or Ribavirin and/or direct antiviral agents (patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA)
For gastric MALT Lymphoma:
For gastric MALT lymphoma, the clinical evidence of the MZL as seen by gastroendoscopy is sufficient. There is no need to show a measurable lesion by CT scan or MRI. Please refer to Appendix E.
Inclusion is possible for patients with:
H. pylori-negative disease de novo or following or being not eligible for local therapy (i.e., surgery, radiotherapy or antibiotics) or after systemic therapy.
H. pylori-positive disease that has remained stable, progressed, or relapsed following antibiotic therapy
Others:
Age = 18 years
Life expectancy > 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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified