Treatment with Ofatumumab for RElapsed/refractory Splenic B-cell marginal zone lymphoma (MORE)

• Conditions: Splenic B-cell marginal zone lymphoma; MedDRA version: 16.1Level: PTClassification code 10062113Term: Splenic marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2013-004916-23-IT
• Lead Sponsor: Ospedale San Raffaele

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02-21
• Last Update Posted: 30 March 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Initial diagnosis of CD20+ Splenic B-cell Marginal Zone Lymphoma (SMZL) confirmed by histology, cytology and immunophenotype and chromosomal abnormalities (WHO 2008 classification)
•For not splenectomised patients: diagnosis on bone marrow biopsy (histology), aspirate (immunophenotype), and peripheral blood (cytology, immunophenotype) according to Matutes et al, Leukemia 2008; chromosomal abnormalities by Quantitative Multiplex PCR Short Fluorescent Fragments (QMPSF) are optional;
•For splenectomised patients: diagnosis on spleen, bone marrow biopsy (histology), aspirate (immunophenotype), and peripheral blood (cytology, immunophenotype) according to WHO 2008 criteria; chromosomal abnormalities by QMPSF are optional
2.Relapsed or Refractory after =2 prior line(s) of chemotherapy (either monotherapy or combinations) or immunochemotherapy (including single-agent rituximab). Antiviral treatment or splenectomy alone is not considered a first-line therapy; elapsed time between splenectomy and disease progression must be at least one year in splenectomised patients.
•Relapse is indicated by at least one of the following conditions:
-Bulky (arbitrarily defined as = 6 cm below the left costal margin) or progressive or painful splenomegaly and not eligible for splenectomy or not willing splenectomy
-one of the following symptomatic/progressive cytopenias: haemoglobin (Hb) <10 g/dL, or platelets (Plt) <80 000 /µL, or absolute neutrophil count (ANC) <1000 /µL, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration)
-enlarged lymphoadenopathy or involvement of extranodal sites with or without cytopenia
•Refractoriness to treatment is defined as failure to respond to previous immuno-, chemo- or immuno-chemotherapy (e.g. stable or progressive disease)
3.Clinically and/or radiologically confirmed measurable disease before treatment start
4.Aged =18 years
5.Eastern Cooperative Oncology Group (ECOG) performance status 0-2
6.Minimum life expectancy of > 6 months
7.Voluntary signed informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
8.ANC =1 000/µL and/or Plt =100 000/µL unless these abnormalities are related to bone marrow infiltration or to hypersplenism
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1. Any type of lymphoma other than SMZL
2. Patients with biopsy-proven high-grade histological transformation
3. Grade 3 or 4 infusion-related reactions during previous rituximab administration requiring treatment discontinuation
4. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy
5. Central Nervous System (CNS) involvement
6. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement by SMZL or stable chronic liver disease per investigator assessment)
7. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
8. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to randomization, congestive heart failure [New York Heart Association (NYHA) III-IV], and arrhythmia unless controlled by therapy with the exception of extra systoles or minor conduction abnormalities
9. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
10. Uncontrolled, active 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
11. Known Human Immunodeficiency virus (HIV) positive serology
12. Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible
13. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient
14. Positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. Positive serology for hepatitis C (HCV) and/or detectable HCV-RNA will not exclude patients from enrollment in absence of signs of liver damage [i.e. alanine aminotransferase (ALT) >2.5 times upper normal limit, total bilirubin >1.5 times upper normal limit] due to HCV-infection
15. Screening laboratory values:
• creatinine >2.0 times upper normal limit or creatinine clearance <30 ml/min
• total bilirubin >1.5 times upper normal limit (unless due to disease involvement of liver or a known history of Gilbert’s disease)
• ALT >2.5 times upper normal limit (unless due to disease involvement of liver)
• alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
16. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening
17. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth con

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To explore the activity of ofatumumab single-agent in patients with relapsed/refractory Splenic B-cell marginal zone lymphoma ;Secondary Objective: To evaluate the safety and tolerability of ofatumumab single-agent in patients with relapsed/refractory Splenic B-cell marginal zone lymphoma;Primary end point(s): Complete Response rate (CR);Timepoint(s) of evaluation of this end point: 1 month after the treatment, every 3 months during the first two years of follow-up and then every 6 months during the third year of follow-up.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Overall Response rate (ORR) <br>- Safety [type, frequency and severity of Adverse Events (AEs) and relationship of AEs to ofatumumab]<br>- Progression-free survival (PFS) <br>- Event-free survival (EFS)<br>- Duration of response (DOR)<br>- Time to next treatment (TTNT)<br>- Overall survival (OS)<br>;Timepoint(s) of evaluation of this end point: During the treatment and during the follow-up.