Obinutuzumab in Marginal Zone Lymphoma
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|ClinicalTrials.gov Identifier: NCT03322865|
Recruitment Status : Recruiting
First Posted : October 26, 2017
Last Update Posted : February 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Marginal Zone Lymphoma||Drug: Obinutuzumab||Phase 2|
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. For efficacy the rate of complete remissions (according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for non-gastric extranodal, nodal and splenic MZL) after induction therapy will be primarily analysed. For toxicity treatment associated adverse events, quality of life and cumulative incidence of secondary malignancies will be documented.
The study is a multicenter, single-arm, open-label, phase II trial of 6 cycles of Obinutuzumab in the induction phase followed by a maintenance phase for a maximum of 12 infusions of Obinutuzumab every 8 weeks in patients aged ≥ 18 years with previously untreated MZL in need of treatment.
The study flow will be as follows:
- Previously untreated patients will be screened for eligibility for the trial. If the patient is eligible for the study, the patient will be registered before the first cycle of induction treatment.
- Patients who progress at any time point during induction are considered as treatment failure. They will be followed up for overall survival until death.
- Patients, who achieve at least a SD after induction treatment will be eligible to receive maintenance therapy with Obinutuzumab.
It is expected that a total of 56 patients at approximately 20 investigator sites will be registered. Every patient will receive treatment over a time period of 6 x 4 weeks, followed by a maintenance phase of every 8 weeks for a maximum of 12 infusions until progression or study drug - related intolerable toxicity. Patient will be monitored every 3 months for 2 additional years, subsequently every 6 months for three additional years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Obinutuzumab in Marginal Zone Lymphoma (OLYMP-1)|
|Actual Study Start Date :||November 23, 2018|
|Estimated Primary Completion Date :||October 2, 2020|
|Estimated Study Completion Date :||May 2, 2024|
Experimental: One Arm
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
Other Name: GA101
- Complete Remission/Response (CR) rate [ Time Frame: 24 weeks ]The complete Response rate (CR) is evaluated after the end of induction
- Progression free survival [ Time Frame: 24 weeks ]Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.
- Overall survival [ Time Frame: participants will be followed for their participation in the trial, an expected average of 8.6 years ]Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.
- Time to first response [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Time to first response is defined as the time from the start of induction to first response (CR, PR).
- Time to best response under treatment (induction and maintenance)Time [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Time to best response is defined as the time from the start of induction to best response the patient achieves (CR, PR).
- Response rate [ Time Frame: 24 weeks ]The response rates (CR, PR) and overall response rate (CR, PR) are evaluated 4 weeks after the end of induction treatment.
- Best response [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Best response is determined in the time interval from the start of induction therapy to end of follow-up.
- Time to Treatment failure [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Time to treatment failure (TTF) is defined as the time of registration to discontinuation of therapy for any reason including death from any cause, progression, toxicity or add-on of new anti-cancer therapy. Patients alive without treatment failure are censored at the latest tumor assessment date.
- Remission duration [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Remission duration will be calculated in patients with response (CR, PR) to induction from end of induction to the date of progression, relapse or death from any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.
- Cause specific survival [ Time Frame: participation will be followed for their participation in the trial, an expected average of 8.6 years ]Cause specific survival is defined as the period from the induction registration to death from lymphoma or lymphoma related cause; death unrelated to MZoL is considered as a competing event.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03322865
|Contact: Stephanie Wölfle, MD||+49731500 ext email@example.com|
|Principal Investigator:||Christian Buske, MD||University Hospital of Ulm|