Reduced-dose radiation therapy for people with follicular or marginal zone lymphoma

A Prospective Phase III Study Comparing Standard Radiotherapy (24 Gy) With a PET REsponse-guided Very Low Dose (4 Gy) Staged Radiotherapy Strategy for Potentially Curable, Indolent B-cell Lymphomas

This trial will test whether very low-dose radiation controls stage I–II follicular or marginal zone lymphoma as well as standard-dose radiation while causing fewer side effects.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 375 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT07029217 on ClinicalTrials.gov

What this trial studies

Adults with localized (stage I–II) follicular or marginal zone lymphoma will be assigned to receive either very low-dose radiation therapy (VLDRT) or the standard radiation dose to the involved sites. The study compares tumor control in the treated areas, the development of new lymphoma sites, and the frequency and severity of short- and long-term side effects between the two dose levels. Radiation is delivered directly to areas of known disease, with VLDRT using a substantially lower total dose than standard treatment. Outcomes will determine whether lower-dose radiation provides comparable disease control with reduced toxicity.

Who should consider this trial

Good fit: Ideal candidates are adults with stage I–II follicular lymphoma or marginal zone lymphoma confined to involved sites who are eligible for definitive radiotherapy according to current pathology classifications (WHO or ICC).

Not a fit: Patients with advanced (stage III–IV) or widely disseminated disease, aggressive lymphoma subtypes, or those who are not candidates for radiotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, patients could achieve effective local disease control with much lower radiation exposure and fewer short- and long-term side effects.

How similar studies have performed: Smaller and nonrandomized studies have shown high local response rates with very low-dose radiation in indolent B-cell lymphomas, but randomized evidence comparing VLDRT to standard-dose therapy for localized disease is limited.

Eligibility criteria

Inclusion Criteria: (Arms 1\&2)

* Patients must be diagnosed with a follicular lymphoma or marginal zone lymphoma. Of note, there are now two widely-utilized pathology classification criteria used for mature B-cell lymphomas, the World Health Organization (WHO) 5th Edition Classification of Lymphoid Neoplasms and the International Consensus Classification (ICC) of Mature Lymphoid Neoplasms. Either criteria is acceptable and for the purposes of this protocol, the following diagnoses are included:

  * Follicular lymphoma

    * WHO 5th Edition

      * Classic follicular lymphoma (cFL)
      * Follicular lymphoma with uncommon features (uFL)
      * Pediatric type follicular lymphoma
      * Duodenal type follicular lymphoma
    * ICC

      * Follicular lymphoma, grades 1-2 or 3A
      * BCL2 rearrangement negative, CD23 positive follicle center lymphoma
      * Pediatric type follicular lymphoma
      * Duodenal type follicular lymphoma
  * Marginal zone lymphoma

    * WHO 5th Edition and ICC

      * Nodal marginal zone lymphoma
      * Pediatric nodal marginal zone lymphoma
      * Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT)
* Patients must have stage I or II disease (with stage I defined as involvement of one nodal region and stage II as two or more nodal regions involved on the same side of the diaphragm)
* Patients should be newly diagnosed or previously observed with no prior lymphoma-directed therapy
* If the patient is referred for localized gastric MALT lymphoma, there should be documented negative H. Pylori testing within 6 months prior to proposed radiotherapy
* Age at the time of enrollment of ≥18 years
* Patients must be able to start radiation within 2 months from time of randomization

Exclusion Criteria:

* Prior radiation to site(s) needing treatment
* Follicular lymphoma, grade 3B (ICC) or Follicular large B cell lymphoma (FLBL by WHO 5th edition criteria)
* Patients planned to receive concurrent systemic therapy (including oral steroids) for their lymphoma
* Patient has cutaneous only iNHL defined as primary cutaneous B-cell lymphoma, primary cutaneous follicle center lymphoma, cutaneous marginal zone lymphoma or unspecified indolent lymphoma of the skin
* Gross total resection of all disease
* Tumor size measuring ≥5 cm in maximum diameter on any modality diagnostic imaging
* Patients with any concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (All Protocol Activities) — Uniondale, New York, United States (Recruiting)

Study contacts

• Principal investigator: Brandon Imber, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Brandon Imber, MD

Conditions Follicular Lymphoma; Marginal Zone Lymphoma; Stage I-II; Radiotherapy; 25-089