Stage II - IV follicular lymphoma grade 1 - 3a and a high tumor burden not previously treated MedDRA version: 20.0 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: 20.0 Level: PT Classification code 10016910 Term: Follicle centre lymphoma, follicular grade I, II, III stage IV System Organ Class: 10029104 - Neoplasms benign
Conditions
Sponsors
Klinikum der Universität München, Medizinische Klinik und Poliklinik III
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 complimentary scientific analyses 2. Ann Arbor Stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease (nodal or extra nodal mass >7 cm) 3. Age = 18 years 4. No prior lymphoma therapy 5. Need for start of therapy as defined by: - bulky disease at study entry according to the GELF criteria (nodal or extra nodal mass >7 cm in its greater diameter) - and/or B symptoms (fever, drenching night sweats, or unintentional weight loss of >10% of normal body weight over a period of 6 months or less) - and/or hematopoietic insufficiency (granulocytopenia 2 cm in its largest dimension by CT scan or MRI) 7. Performance status =2 on the ECOG scale 8. 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. 9. Women are not breast feeding, are using highly effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 18 months thereafter (pregnancy testing is mandatory for premenopausal women) 10. Men agree not to father a child during participation in the trial and during the 18 months thereafter 11. 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 49 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 49
Exclusion criteria
Exclusion criteria: 1. Transformation to high-grade lymphoma (secondary to “low grade” FL) 2. Grade 3b follicular lymphoma 3. Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma). 4. Known hypersensitivity to any of the study drugs 5. Known sensitivity to murine products 6. Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to 2x upper normal value and/or creatinine clearance 3x normal or bilirubin > 2.0 mg/dl (unless caused by known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome]). 10. 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. 11. 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. 12. Known history of HIV seropositive status 13. Patients with a history of confirmed PML 14. Vaccination with a live vaccine within 28 days prior to registration 15. Recent major surgery (within 4 weeks prior to the start of Cycle 1) 16. History of stroke or intracranial hemorrhage within 6 months prior to registration 17. 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) 18. Treatment within a clinical trial within 30 days prior to trial entry 19. Prior organ, bone marrow or peripheral blood stem cell transplantation 20. Known or persistent abuse of medication, drugs or alcohol 21. 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 ibrutinib and obinutuzumab (GA 101) in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Primary endpoint is the rate 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: Overall survival, complete response rate, overall response rate ORR and SD rates at end of induction, one year after start of therapy and after end of maintenance therapy, PFS (continuous observation), duration of response, 3-year-PFS, percentage of progression during induction and during maintenance therapy, percentage of progression during induction and during maintenance therapy, safety, percentage of MRD negative patients during induction therapy (midterm), after induction therapy and after maintenance therapy, duration of molecular remission for MRD negative patients after the end of induction and after end of maintenance, rate of secondary transformation to aggressive lymphoma, time to next anti-lymphoma therapy and time to next chemotherapy based treatment, percentage of secondary malignancies, time to first secondary malignancy, percentage of patients with compliance to therapy after 1, 2 and 3 years and patient-reported lymphoma symptoms and concerns as measured by FACT-Lym. ;Primary end point(s): Progression-free survival (PFS) is chosen as primary endpoint for most phase III trials in FL, since it represents beside overall survival the most clinical relevant parameter for patients. PFS is in this trial defined as the time from registration to lymphoma progression or death from any cause. Since an early readout for efficacy is needed in this phase II trial, the rate of pa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of patients achieving a progression free survival of more than three years - Progression free survival after start of therapy (continuous observation) - CR, PR and SD rates after induction therapy, one year after start of therapy and after end of maintenance therapy (at 30 months after start of therapy: CR30) - Duration of Response - Percentage of progression during induction and during maintenance therapy - Time to treatment failure after start of therapy (failure defined by missing CR/PR or progression after CR or PR or death in remission) - Time to next anti-lymphoma therapy and time to next chemotherapy based treatment - Safety including treatment associated adverse events - Percentage of MRD negative patients during induction therapy (midterm), after induction therapy and after maintenance therapy - Duration of molecular remission for MRD negative patients after the end of induction and after end of maintenance - Percentage of secondary transformation to aggressive lymphoma - Percentage of secondary malignancies - Time to first secondary malignancy - Overall survival - Percentage of patients with compliance to therapy after 1, 2 and 3 years - 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 censored at the last documented event-free observation. | — |
Countries
Germany
Contacts
Public ContactDr. rer. nat. Michael Unterhalt
Klinikum der Universität München - Medizinische Klinik und Poliklinik III - Leitung der Studienzentrale für Hämatologie
Outcome results
None listed