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Copanlisib and Rituximab in Marginal Zone Lymphoma Patients - A MULTICENTER OPEN LABEL SINGLE-ARM PHASE II STUDY (COUP-1)
EU CTIS ID: 2022-500674-34-00
What this study is testing
The objective of the trial is to test the efficacy and toxicity of treatment with Copanlisib and Rituximab in patients with MZL in need of treatment, who have failed or are not eligible for local therapy or relapsed. 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) at 12 month therapy will be primarily analysed. For toxicity treatment associated adverse events, quality of life and cumulative incidence of secondary malignancies will be documented.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Confirmed CD20 positive MALT Lymphoma de novo or relapsed following or being not eligible for local therapy (including surgery, radiotherapy) and antibiotics for H. pylori-positive gastric lymphoma arisen at any extranodal site. OR
- Life expectancy >3 months
- Baseline platelet count >=50 G/L (if not due to BM infiltration by the lymphoma), absolute neutrophil count >=0.75 G/L
- ASAT (SGOT): <=3 times the upper limit of institutional laboratory normal value
- ALAT (SGPT): <=3 times the upper limit of institutional laboratory normal value
- Total Bilirubin: <=2 mg/dL or 2 times the upper limit of institutional laboratory normal value, unless clearly related to the disease (except if due to Gilbert’s syndrome)
You likely can't join if
- ECOG performance status ≥ 2
- Prior treatment with Copanlisib
- Congestive heart failure > New York Heart Association (NYHA) class 2
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
- Myocardial infarction less than 6 months before start of test drug
- Uncontrolled arterial hypertension despite optimal medical management
See the full eligibility criteria
Who can join
- Confirmed CD20 positive MALT Lymphoma de novo or relapsed following or being not eligible for local therapy (including surgery, radiotherapy) and antibiotics for H. pylori-positive gastric lymphoma arisen at any extranodal site. OR
- Life expectancy >3 months
- Baseline platelet count >=50 G/L (if not due to BM infiltration by the lymphoma), absolute neutrophil count >=0.75 G/L
- ASAT (SGOT): <=3 times the upper limit of institutional laboratory normal value
- ALAT (SGPT): <=3 times the upper limit of institutional laboratory normal value
- Total Bilirubin: <=2 mg/dL or 2 times the upper limit of institutional laboratory normal value, unless clearly related to the disease (except if due to Gilbert’s syndrome)
- GFR ≥ 40 mL/min/1.73 m²
- Negative HIV antibody
- Positive test results for chronic HBV infection (defined as positive HBsAg serology): patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible.
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing): patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- Pregnancy β-HCG negative. For women of child-bearing potential only (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy); serum or urine β-HCG must be negative during screening and at study enrolment visit
- Confirmed CD20 positive de novo or relapsed splenic MZL following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus) with symptomatic disease: In patients with splenic MZL without splenic tissue available for histologic review, the diagnosis may be confirmed by the presence of splenomegaly and typical morphologic and immunophenotypic findings in the blood and bone marrow. Bone marrow (acceptable up to 12 weeks before start of treatment) must be submitted for retrospective central confirmation. OR
- Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy up to 12 months after end of therapy.
- Men must agree not to father a child for the duration of therapy and 6 months after (use of a condom) and must agree to advice a female partner to use a highly effective method of birth control.
- Willingness and ability to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions.
- Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.
- Confirmed CD20 positive de novo or relapsed nodal MZL
- Tissue diagnostic procedures must be performed within 12 months prior to study entry and have to include diagnostics by a reference pathology center.
- 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 nodal MZL and EMZL: At least one bi-dimensionally measurable lesion (≥ 1.5 cm in its largest dimension by CT scan or MRI)
- For SMZL: For splenic MZL, an enlarged spleen on CT scan and lymphoma cell infiltration has to be seen in bone marrow and/or peripheral blood. At least one of the following criteria 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) – SMZL with concomitant hepatitis C infection which has not responded to or has relapsed after Interferon and/or Ribavirin and/or direct antiviral agents (patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA). – splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites if not being eligible for local therapy.
- For gastric MALT lymphoma, the clinical evidence of the MZL as seen by gastroendoscopy is sufficient. There is no need to show a measurable lesion by CT scan or MRI. Inclusion is possible for patients with: a) H. pylori-negative disease de novo or following or being not eligible for local therapy (i.e., surgery, radiotherapy or antibiotics) or after systemic therapy. b) H. pylori–positive disease that has remained stable, progressed, or relapsed following antibiotic therapy.
- Age >=18 years
What rules you out
- ECOG performance status ≥ 2
- Prior treatment with Copanlisib
- Congestive heart failure > New York Heart Association (NYHA) class 2
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
- Myocardial infarction less than 6 months before start of test drug
- Uncontrolled arterial hypertension despite optimal medical management
- HbA1c>8.5%
- 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
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
- 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.
- Non-healing wound, ulcer, or bone fracture
- History or concurrent interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
- 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 enrolment visit
- Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
- Ongoing alcohol or drug addiction
- 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
- Breastfeeding or pregnancy
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.