Obinutuzumab in Marginal Zone Lymphoma

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

Interventions

DRUG

Obinutuzumab

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

Sponsors & Collaborators

• University of Ulm

  collaborator OTHER

• Optimapharm

  collaborator INDUSTRY

• Zentrum für Klinische Studien Ulm

  collaborator OTHER

• X-act Cologne Clinical Research GmbH

  collaborator INDUSTRY

• Roche Pharma AG

  collaborator INDUSTRY

• Christian Buske

  lead OTHER

Principal Investigators

• Christian Buske, MD · University Hospital of Ulm

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-11-23

Primary Completion

2027-01-31

Completion

2027-01-31

Countries

• Germany

Study Locations