OBINUTUZUMAB in MARGINAL ZONE LYMPHOMA

Phase 1

Conditions: Marginal Zone Lymphoma
MedDRA version: 21.0Level: PTClassification code 10062113Term: Splenic marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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: EUCTR2017-003149-56-DE

Lead Sponsor: niversity Hospital Ulm

Brief Summary: Not available

Detailed Description: Not available

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 MZoL, diagnosed by a reference pathology center.
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
Confirmed CD20 positive de novo MALT Lymphoma 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
ORConfirmed CD20 positive de novo splenic MZoL following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus) with symptomatic disease
OR Confirmed CD20 positive de novo nodal MZoL following or not being eligible for local therapy (radiotherapy)
For patients with symptomatic splenic, nodal, or non-gastric extranodal MZoL disease that is de novo or has relapsed following local therapy (i.e., surgery or radiotherapy) and requires therapy, as assessed by the investigator.
For patients with symptomatic gastric extranodal MZoL: Helicobacter pylori-negative disease that is de novo or has relapsed following local therapy (i.e., surgery or radiotherapy) and requires therapy, as assessed by the investigator, or H. pylori–positive disease that has remained stable, progressed, or relapsed following antibiotic therapy and requires therapy, as assessed by the investigator
–At least one bi-dimensionally measurable lesion (= 1.5 cm in its largest dimension by CT scan or MRI).
For an enlarged liver to constitute the only measurable disease parameter, a liver biopsy showing proof of NHL in the liver is required.
For SMZL:
In patients with splenic MZoL, an enlarged spleen on CT scan or extending at least 2 cm below the costal margin by physical examination will constitute measurable disease providing that no explanation other than lymphomatous involvement is likely.
At least one of the following must be met:
–Bulky progressive or painful splenomegaly
–one of the following symptomatic/progressive cytopenias : Hb < 10 g/dL, or Plat < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration)
–enlarged lymphoadenopathy or involvement of extranodal sites with or without cytopenia
–splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites
–SMZL with concomitant hepatitis C infection who have not responded to or are relapsed after Interferon and/or Ribavirin (patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
For gastric MALT Lymphoma:
–H. pylori-negative disease de novo or following or being not eligible for local therapy (i.e., surgery, radiotherapy or antibiotics).
–H. pylori–positive disease that has remained stable, progressed, or relapsed following antibiotic therapy.

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 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

–ECOG performance status >2
–History of a non-lymphoid 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 enrollment visit, other Stage 1 or 2 cancer 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.
–Ongoing immunosuppressive therapy including corticosteroids (exception < 4 weeks administered at a dose equivalent to <=40 mg/day prednisone is allowed)
–Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of study enrollment visit
–Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
–Ongoing alcohol or drug addiction
–Breastfeeding or pregnancy
–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.
–History of anaphylaxis in association with previous administration of monoclonal antibodies.
–Vaccination with a live vaccine within 28 days prior to start of therapy
–Treatment with any other investigational agent within 30 days or within 5 x the half-life (t1/2) of the investigational product, whichever is longer, or participating in another trial within 30 days prior to entering this study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the trial is to test the efficacy and toxicity of first line treatment with single agent Obinutuzumab in patients with MZoL in need of treatment, who have failed or are not eligible for local therapy. ;Secondary Objective: •Progression free survival <br>•OR rates, PR rates<br>•Duration of response<br>•Time to first response<br>•Time to best response under treatment (induction and maintenance)<br>•Time to next anti-lymphoma therapy and time to next chemotherapy based treatment<br>•Treatment associated adverse events<br>•Quality of life during induction and maintenance therapy<br>•Cumulative incidence of secondary malignancies<br>•Cumulative incidences of disease related death<br>•Overall survival<br>;Primary end point(s): CR rate (CRR) (determined after induction therapy);Timepoint(s) of evaluation of this end point: Determined after induction therapy

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Progression free survival <br>•OR rates, PR rates<br>•Duration of response<br>•Time to first response<br>•Time to best response under treatment (induction and maintenance)<br>•Time to next anti-lymphoma therapy and time to next chemotherapy based treatment<br>•Treatment associated adverse events<br>•Quality of life during induction and maintenance therapy<br>•Cumulative incidence of secondary malignancies<br>•Cumulative incidences of disease related death<br>•Overall survival<br>;Timepoint(s) of evaluation of this end point: Induction and Maintenance

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