Follicular Lymphoma with high tumor burden (grade 1- 3a, Ann Arbour stage II - IV, previously untreated) MedDRA version: 21.1 Level: PT Classification code 10016908 Term: Follicle centre lymphoma, follicular grade I, II, III stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10016909 Term: Follicle centre lymphoma, follicular grade I, II, III stage III System Organ Class: 10029104 - Neop
Conditions
Interventions
Product Name: Copanlisib
Product Code: BAY 80-6946
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: COPANLISIB
Current Sponsor code: BAY 80-6946
Concentration unit: mg
Sponsors
Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses - Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease - Age = 18 years - No prior lymphoma therapy - Need for start of therapy as defined by at least one of the following criteria: bulky disease at study entry according to the GELF criteria (nodal or extranodal mass > 7 cm in its greater diameter) B symptoms (fever, drenching night sweats, or unintentional weight loss of > 10% of normal body weight over a period of 6 months or less) hematopoietic insufficiency (granulocytopenia 2 cm in its largest dimension by CT scan or MRI) - Performance status = 2 on the ECOG scale - Adequate hematologic function (unless abnormalities are related to NHL), defined as follows: Hemoglobin = 9.0 g/dL absolute neutrophil count = 1500/µl Platelet count = 75000/µl - Women are not breast feeding, are using highly effective contraception (see section 11.4.1), are not pregnant, and agree not to become pregnant during study treatment and for 18 months after last application of Obinutuzumab and for one month after last application of Copanlisib (pregnancy testing is mandatory for premenopausal women). - Men agree not to father a child during study treatment and for 18 months after last application of Obinutuzumab and for one month after last application of Copanlisib. - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Transformation to high-grade lymphoma (secondary to “low grade” FL) - Grade 3B follicular lymphoma - Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma) - Known hypersensitivity to any of the study drugs - Known sensitivity to murine products - Patients with HbA1c > 8.5 % at Screening - Uncontrolled arterial hypertension despite optimal medical management (per investigator’s assessment) - Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to 2x normal value and/or creatinine clearance 3x normal or bilirubin > 2.0 mg/dl (unless caused by known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome]) - 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 hepatitis B surface antibody (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. - Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis - Known history of HIV seropositive status - Patients with a history of confirmed PML - Vaccination with a live vaccine within 28 days prior to registration - Recent major surgery (within 4 weeks prior to the start of Cycle 1) - History of stroke or intracranial hemorrhage within 6 months prior to registration - Serious underlying medical conditions, which could impair the ability of the patient to undergo the treatment offered in the study (e.g. ongoing infection, gastric ulcers, active autoimmune disease) - Treatment within a clinical study within 30 days prior to study entry - Prior organ, bone marrow, or peripheral blood stem cell transplantation - Known or persistent abuse of medication, drugs, or alcohol - Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of the chemotherapy-free combination of copanlisib and obinutuzumab in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Primary endpoint is the probability of progression free survival one year after registration. Progression-free survival (PFS) is chosen as primary endpoint since it represents besides overall survival the most relevant parameter for patients. PFS is defined as the time from registration to lymphoma progression or death from any cause.;Secondary Objective: • Complete remission (CR) rates and overall response rates at end of induction, at end of consolidation and at end of maintenance • Progression free survival from registration • Duration of response from end of induction to progression/death • Cumulative incidence of progression from registration • Failure-free survival from start of therapy • Time to next anti-lymphoma therapy/time to next chemotherapy • Overall survival from registration • Treatment associated adverse events • Percentage of MRD-negative patients • Duration of molecular remission for MRD negative patients from end of induction therapy • Cumulative incidence of secondary transformations to aggressive lymphoma • Cumulative incidence of secondary malignancies • Percentage of patients with compliance to therapy after 6, 12, and 30 months • Frequency of patient-reported lymphoma symptoms and concerns (FACT-Lym);Primary end point(s): One-year progression-free survival (PFS) probability from study registration.;Timepoint(s) of evaluation of this end point: One year after registration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Complete remission (CR) rates and overall response (CR or partial remission, PR) rates at end of induction (month 6), at end of consolidation (month 12), and at end of maintenance (month 30) • Progression free survival from registration (continuous observation) • Duration of response from end of induction to progression or death • Cumulative incidence of progression from registration • Failure-free survival from start of therapy (event defined by failure to achieve a CR/PR after 6 months or progression after CR or PR or death from any cause) • Time to next anti-lymphoma therapy and time to next chemotherapy based treatment from start of first-line therapy • Overall survival from registration • Treatment associated adverse events • Percentage of MRD-negative patients at midterm induction, at end of induction therapy (month 6), at end of consolidation therapy (month 12), and at end maintenance therapy (month 30) • Duration of molecular remission for MRD negative patients from end of induction therapy • Cumulative incidence of secondary transformations to aggressive lymphoma • Cumulative incidence of secondary malignancies • Percentage of patients with compliance to therapy after 6, 12, and 30 months • Frequency of patient-reported lymphoma symptoms and concerns (FACT-Lym);Timepoint(s) of evaluation of this end point: The time to event parameters survival, progression free survival, time to treatment failure, time to first secondary malignancy and time to next anti-lymphoma therapy/chemotherapy will be evaluated starting at registration in this trial. If an event has not been observed at evaluation, the parameter will be monitored at the last documented event-free observation. | — |
Countries
Germany
Contacts
Public ContactDr. med. Michael Unterhalt
Klinikum der Universität München
Outcome results
None listed