Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma

1. Histologically documented diagnosis of CD20+ Follicular lymphoma grade 1-2 or 3a, as defined in the 2017 edition of the World Health Organization (WHO) classification;

2. Age ≥ 18 years;

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix B);

4. No previous immunochemotherapy for the lymphoma (localized radiotherapy or rituximab monotherapy with max of 4 doses are allowed);

5. Ann Arbor stage II-IV (Appendix A);

6. High tumor burden as per Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria defined as the presence of at least one of the following:

* systemic symptoms;

* Tumor bulk (any nodal or extranodal tumor mass with diameter \> 7 cm);

* involvement of ≥ 3 nodal sites, each with a diameter ≥ 3 cm;

* splenomegaly;

* compressive syndrome (organ compression);

* serous effusion;

* circulant malignant cells;

* cytopenia;

* Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) \> 1;

* Lactate dehydrogenase (LDH) \> upper limit of normality (ULN);

* β2-microglobulin \> 3 mg/L.

7. At least one site of measurable nodal disease at baseline ≥ 1.5 cm in the longest transverse diameter as determined by CT scan (MRI is allowed if CT scan cannot be performed); or evaluable disease at baseline FDG-PET (18F-fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)) scan (at least one metabolic active site of disease);

8. Adequate hematological counts (unless due to bone marrow involvement by lymphoma) defined as follows:

1. Absolute Neutrophil count (ANC) \> 1.5 x 109/L;

2. Platelet count ≥ 80 x 109/L ;

3. Hemoglobin ≥ 10 g/dL.

9. Adequate renal function defined as creatinine ≤ 2 mg/dL, unless secondary to lymphoma;

10. Adequate hepatic function defined as bilirubin ≤ 2 mg/dL, unless secondary to lymphoma;

11. Left Ventricular Ejection Fraction (LVEF) \> 50% at bidimensional echocardiogram (mandatory only for patients receiving R/G-CHOP);

12. Life expectancy ≥ 6 months;

13. Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures;

14. Subject must be able to adhere to the study visit schedule and other protocol requirements;

15. Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 12 months after last rituximab dose or 18 months after last obinutuzumab dose. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1%) e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner. The use of condoms by male patients is required (even if surgically sterilized, i.e., status post vasectomy) unless the female partner is permanently sterile. Full sexual abstinence is admitted when this is in line with the preferred and usual lifestyle of the subject, for the same time period planned for other methods of birth control (see above). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner) and withdrawal are not acceptable methods of contraception).

What this study is about