Copanlisib and Rituximab in Marginal Zone Lymphoma Patients
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|ClinicalTrials.gov Identifier: NCT03474744|
Recruitment Status : Not yet recruiting
First Posted : March 23, 2018
Last Update Posted : March 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Marginal Zone Lymphoma||Drug: Copanlisib||Phase 2|
For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy is 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 PI3K inhibitor Copanlisib has shown high clinical activity in indolent B - cell lymphomas among them MZL. Based on these observations it is the aim of this study to test the toxicity and efficacy of Copanlisib in combination with the anti-CD20 antibody Rituximab in patients with newly diagnosed or relapsed MZL in need of treatment, who are not eligible or failed local therapy, following the assumption that this novel chemotherapy - free combination is significantly more effective than Rituximab single agent therapy and at least as efficient as Rituximab/chemotherapy, but avoids chemotherapy - related toxicity.
The objective of the trial is to test the efficacy and toxicity of the treatment of Copanlisib/Rituximab in patients with MZL in need of treatment, who have failed or are not eligible for local therapy or relapsed after local or systemic therapy. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Copanlisib and Rituximab in Marginal Zone Lymphoma Patients (COUP-1)|
|Estimated Study Start Date :||June 1, 2018|
|Estimated Primary Completion Date :||June 1, 2018|
|Estimated Study Completion Date :||December 1, 2026|
Experimental: Experimental Arm
Copanlisib 60 mg i.v. fixed dose days 1,8,15 Rituximab 375 mg/m2 day 1 i.v.
Induction Phase Cycle 1-6 (28 days cycle):
60 mg i.v. fixed dose days 1, 8, 15.
375 mg/m2 day 1 i.v.
Other Name: Rixathon
- Complete Response [ Time Frame: 12 months ]Primary endpoint is the complete response (CR rate (CRR) determined 12 months after start of induction therapy). Patients who progress before 12 months after start of treatment will be treated as CR='NO' and will be included in the calculation of the primary endpoint. No primary endpoint will be determined for patients who withdraw.
- Response rate [ Time Frame: 12 months ]The response rates (complete response (CR), partial response (PR)) and overall response rate (CR or PR) are evaluated 4 weeks after the end of induction treatment and 12 months after start of treatment.
- Best response [ Time Frame: 8.5 years ]Best response is determined in the time interval from the start of induction therapy to end of follow-up.
- Time to best response [ Time Frame: 8.5 years ]Time to best response is defined as the time from the start of induction to best response the patient achieves (CR, PR).
- Time to first response [ Time Frame: 12 months ]Time to first response is defined as the time from the start of induction to first response (CR, PR).
- Progressioin free survival (PFS) [ Time Frame: 12 months ]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.
- Time to Treatment failure (TTF) [ Time Frame: 8.5 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.
- Duration of Response (DR) [ Time Frame: 8.5 years ]Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.
- Cause specific survival (CSS) [ Time Frame: 8.5 years ]Cause specific survival is defined as the period from the induction registration to death from lymphoma or lymphoma related cause; death unrelated to MZL is considered as a competing event.
- Overall survival (OS) [ Time Frame: 8.5 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.
- Quality of life during induction and maintenance therapy [ Time Frame: 8.5 years ]Quality of life will be measured by the FACTLym before start of treatment, during induction and maintenance.
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): NCT03474744
|Contact: Christian Buske, MD||+49731500 ext email@example.com|