Obinutuzumab in Marginal Zone Lymphoma

NCT03322865 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: OLYMP-12017-003149-56
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 12

Brief Summary

For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy are widely used for those patients who fail local therapy or do not qualify for such. Depending on the MZL subtype Rituximab/chemotherapy is able to induce in part long remissions, but do not prevent relapse later on. In addition, chemotherapy associated toxicity is often problematic in MZL patients, who are mostly of advanced age. Thus, chemotherapy - free approaches are highly attractive for this patient group. Rituximab single agent is a widely used chemotherapy - free approach in MZL, but was significantly inferior compared to Rituximab/chlorambucil in a large randomized prospective clinical trial in treatment naïve MZL with a CR rate of 56 % vs. 80%, respectively (P\<0.001).Thus, it is the major aim to develop chemotherapy - free approaches for MZL, which approach efficacy of rituximab/chemotherapy combinations, but avoid chemotherapy associated toxicities. This in particular important in MZL as many physicians are reluctant to treat these often elderly patients with more intense treatments and prefer single agent therapies in these very often well and long responding lymphoma subtype. The type II anti-CD20 antibody Obinutuzumab (OBINUTUZUMAB) has demonstrated remarkable activity in follicular lymphoma and superiority to Rituximab in combination with chemotherapy in treatment naïve (Gallium trial) and rituximab refractory follicular lymphoma (Gadolin trial) as well as in CLL in combination with chlorambucil. Based on these observations it is the aim of this study to test the toxicity and efficacy of the anti-CD20 antibody Obinutuzumab (OBINUTUZUMAB) in patients with newly diagnosed MZL in need of treatment, who are not eligible or failed local therapy, following the assumption that this novel anti-CD20 antibody is significantly more effective than Rituximab single agent therapy, and avoids chemotherapy - related toxicity.

Conditions

Marginal Zone Lymphoma

Keywords

Obinutuzumab; Anti-CD20 antibody; Oncology

Outcome Measures

Primary Outcomes (1)

• Complete Remission/Response (CR) rate

  The complete Response rate (CR) is evaluated after the end of induction

  24 weeks

Secondary Outcomes (9)

• Progression free survival

  24 weeks

• Overall survival

  participants will be followed for their participation in the trial, an expected average of 8.6 years

• Time to first response

  participation will be followed for their participation in the trial, an expected average of 8.6 years

• Time to best response under treatment (induction and maintenance)Time

  participation will be followed for their participation in the trial, an expected average of 8.6 years

• Response rate

  24 weeks

Study Arms (1)

One Arm

EXPERIMENTAL

Obinutuzumab i.v.

Drug: Obinutuzumab

Interventions

Obinutuzumab DRUG

Induction: Cycle 1 (28 days cycle): Obinutuzumab (OBINUTUZUMAB) 1000mg i.v. fixed dose day 1,8,15\* \*In the case of suspected increased risk of severe IRR, the dose of obinutuzumab may be 100 mg intravenously on day 1 in cycle 1, 900 mg on day 2. Cycle 2-6 (28 days cycle): Obinutuzumab (OBINUTUZUMAB) 1000mg i.v. fixed dose day 1 Maintenance Start 8 weeks after the last induction cycle for patients at least achieving a partial response after induction: Obinutuzumab (OBINUTUZUMAB) 1000mg i.v. fixed dose day 1 every 8 weeks for a maximum of 12 infusions unless progression or study drug - related intolerable toxicity

Also known as: GA101

One Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a proven pathological diagnosis of MZL.
• Confirmed CD20 positive de novo MALT Lymphoma following or being not eligible for local therapy (including surgery, radiotherapy) and antibiotics for H. pylori-positive gastric lymphoma arisen at any extranodal site
• Confirmed CD20 positive de novo splenic MZL following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus) with symptomatic disease
• Confirmed CD20 positive de novo nodal MZL
• Patients in need of treatment:
• For patients with symptomatic splenic, nodal, or non-gastric extranodal MZL 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 MZL: 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 (\> 2 cm in its largest dimension by CT scan or MRI).
• In patients with splenic MZL, 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. 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:
• Bulky progressive or painful splenomegaly
• one of the following symptomatic/progressive cytopenias : Hb \< 10 g/dL, or Plat \< 80.000 /microL, or neutropenia \< 1000 /microL, 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:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrolment:
• 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.
• Ann Arbor Stage I disease
• Ongoing immunosuppressive therapy other than corticosteroids
• 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
• Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
• 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

Sponsors & Collaborators

• Zentrum für Klinische Studien Ulm: collaborator
• X-act Cologne Clinical Research GmbH: collaborator
• Roche Pharma AG: collaborator
• Christian Buske: lead
• University of Ulm: collaborator
• Optimapharm: collaborator

Study Sites (12)

Augusta-Kranken-Anstalt gGmbH

Bochum, 44791, Germany

Location

University Hospital Essen

Essen, 45147, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsmedizin Georg-August-University

Göttingen, 37075, Germany

Location

University Hospital Halle

Halle, 06120, Germany

Location

Institut für Versorgungsforschung GbR

Koblenz, 56068, Germany

Location

University Hospital Mainz

Mainz, 55101, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, 48149, Germany

Location

University Hospital Münster

Münster, 48149, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

Related Publications (1)

• Grunenberg A, Kaiser LM, Woelfle S, Schmelzle B, Viardot A, Moller P, Barth TF, Muche R, Dreyhaupt J, Buske C. Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma. Future Oncol. 2020 May;16(13):817-825. doi: 10.2217/fon-2020-0071. Epub 2020 Mar 30.

  PMID: 32223334 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Neoplasms

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Christian Buske, MD

  University Hospital of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 26, 2017
• Study Start: November 23, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

DE (12)