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Comparing shortened and standard chemotherapy with immunotherapy for high tumor burden follicular lymphoma

Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma. A Randomized, Open Label, Phase III Study by Fondazione Italiana Linfomi.

Phase 3 Interventional Fondazione Italiana Linfomi - ETS · NCT05058404

This study is testing if a shorter chemotherapy treatment can work just as well as the standard treatment for people with newly diagnosed, advanced follicular lymphoma that has a high tumor burden.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment602 (estimated)
Ages18 Years and up
SexAll
SponsorFondazione Italiana Linfomi - ETS Academic / other
Drugs / interventionsrituximab, obinutuzumab, chemotherapy, immunotherapy, radiation
Locations71 sites (Barletta, Barletta Andria Trani and 70 other locations)
Trial IDNCT05058404 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, multicenter, randomized phase III trial designed to evaluate the effectiveness of a shortened chemotherapy regimen in patients with newly diagnosed, advanced stage follicular lymphoma and high tumor burden. Participants will be randomly assigned to receive either standard chemotherapy or a reduced number of chemotherapy cycles based on their response to initial treatment. The study aims to determine if the shortened regimen is as effective as the standard treatment in terms of progression-free survival. The trial will utilize various approved immunochemotherapy regimens tailored to individual patient needs.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of high tumor burden follicular lymphoma.

Not a fit: Patients with low tumor burden or those who have previously received immunochemotherapy for lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a less intensive treatment option for patients, potentially reducing side effects while maintaining effectiveness.

How similar studies have performed: Other studies have explored similar approaches in lymphoma treatment, showing promising results, but this specific comparison of shortened versus standard chemotherapy in this context is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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).

Exclusion Criteria:

1. Histological diagnosis different from FL grade 1-3a WHO 2017 classification;
2. Suspect or clinical evidence of Central Nervous System (CNS) involvement by lymphoma;
3. Contraindication to the use of anti-CD20 monoclonal antibodies;
4. Subject has received any anticancer therapy (chemotherapy, immunotherapy, investigational therapy, including targeted small molecule agents) within 14 days prior to the first dose of study drug;
5. Noteworthy history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent;
6. Any history of other active malignancies within 3 years prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uterine; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; limited stage surgically removed breast cancer or adequately treated with radiation therapy; limited stage prostate carcinoma surgically removed or adequately treated with radiation therapy; previous malignancy confined and surgically resected with curative intent;
7. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

   * Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
   * Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if Polymerase Chain Reaction (PCR) negative for HCV-RNA;
8. Women who are pregnant or breastfeeding.

Where this trial is running

Barletta, Barletta Andria Trani and 70 other locations

+21 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Follicular LymphomaHigh tumor burden Follicular LymphomaShortened vs standard chemotherapyImmunotherapyInitial treatment
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.