Reduced Dose Radiotherapy for the Treatment of Indolent Non-Hodgkin Lymphoma

MC230808 Reduced Dose Hypofractionated Radiotherapy (3Gy x 3 Fractions) for Indolent Non-Hodgkin Lymphoma (POSEIDON): A Multisite Phase 2 Randomized Trial

This phase II trial compares the safety, side effects and effectiveness of reduced dose radiation therapy to standard of care dose radiation in treating patients with indolent non-Hodgkin lymphoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Standard of care radiation treatment for indolent non-Hodgkin lymphoma is usually delivered in 12 treatments. Studies have shown indolent lymphoma to be sensitive to radiation treatment, however, larger doses have higher rates of toxicities. A reduced radiation dose may be safe, tolerable and/or effective compared to standard of care radiation dose in treating patients with indolent non-Hodgkin lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Indolent B-Cell Non-Hodgkin Lymphoma; Recurrent Indolent Non-Hodgkin Lymphoma; Refractory Indolent Non-Hodgkin Lymphoma; Recurrent Indolent B-Cell Non-Hodgkin Lymphoma; Refractory Indolent B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Endoscopic Procedure; Radiation: Involved-site Radiation Therapy (3 Fractions); Radiation: Involved-site Radiation Therapy (12 Fractions)

Detailed Description

PRIMARY OBJECTIVE:

I. To show that the experimental arm [9 gray (Gy) in 3 fractions, 8 Gy in 2 fractions, or 10 Gy in 5 fractions] has significantly reduced acute toxicity (grade ≥ 2 adverse events at least possibly related to radiation treatment within 14 days after the end of radiation treatment [according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0] compared to 24 Gy in 12 fractions.

SECONDARY OBJECTIVES:

I. To evaluate patient reported quality of life. II. To evaluate response rate. III. To evaluate local control rate. IV. To evaluate relapse-free survival.

EXPLORATORY OBJECTIVES:

I. Financial toxicity will be assessed at the end of radiation treatment. II. Financial health care expenditure will be assessed at the end of radiation treatment III. Late toxicity.

CORRELATIVE RESEARCH OBJECTIVES:

I. Biopsies of enrolled patients will be evaluated for pathological assessment of cellular and genetic mutations to correlate them with disease local relapse and radiation resistance.

II. Patients will have their baseline positron emission tomography (PET)/computed tomography (CT) scan undergo auto-segmentation to calculate the functional imaging 18-fluoro-deoxyglucose (FDG) metabolic tumor volume (MTV), total lesions glycolysis (TLG) and maximum standardized uptake volume (SUVmax) of the sites to be treated with involved-site radiation therapy (ISRT) using MIMvista platform to correlate it with disease local relapse and treatment response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo reduced dose ISRT once daily (QD) over 3, 2, or 5 treatment fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.

ARM II: Patients undergo standard of care (SOC) radiation therapy QD over 12 treatment fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.

After completion of study treatment, patients are followed up at days 7 and 14, months 3 and 6, and then every 6 months for up to 2 years post-radiation therapy.

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: William G. Rule, MD
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Brad S. Hoppe, MD, MPH
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Recruiting
      • Mayo Clinic Health System in Albert Lea
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: John Yeakel, MD
    • Mankato, Minnesota, United States, 56001
      • Recruiting
      • Mayo Clinic Health System - Mankato
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Jason T. Hayes, MD
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Scott C. Lester, MD
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Recruiting
      • Mayo Clinic Health System-Eau Claire Clinic
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Now Bahar Alam, MD
    • La Crosse, Wisconsin, United States, 54601
      • Recruiting
      • Mayo Clinic Health System-Franciscan Healthcare
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Abigail L. Stockham, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years

• Histological confirmation of indolent B-cell lymphoma that can include any of the following:

  • Follicular lymphoma (grade 1 or 2 or 3A)
  • Marginal zone lymphoma (nodal or extranodal)
  • Follicle center lymphoma
• Any stage disease
• Initial, refractory, or relapsed disease. If relapse involves the site to be treated there must be evidence of disease progression
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Ability to complete questionnaire(s) by themselves or with assistance
• Willing to return to enrolling institution for follow-up visits (during the active monitoring phase of the study). Virtual visits can also be considered as an option for applicable items
• Confirmation from radiation oncologist of suitability to participate in study

Exclusion Criteria:

• Any of the following:

  • Pregnant women
  • Nursing women
  • Women of childbearing potential who are unwilling to employ adequate contraception
• T-cell lymphoma
• Receiving treatment for small and chronic lymphocytic lymphoma
• Grade 3B follicular lymphoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1 (reduced dose ISRT); Patients undergo reduced dose ISRT once daily (excluding weekends): 9 Gy delivered in 3 treatment fractions or 8 Gy in 2 fractions. At physician discretion, patients may receive 10 Gy in 5 fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.	Other: Questionnaire Administration; Ancillary studies; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Endoscopic Procedure; Undergo endoscopy; Other Names: ES; Endoscopy; Endoscopic Examination; Radiation: Involved-site Radiation Therapy (3 Fractions); Undergo ISRT in 3 fractions; Other Names: ISRT
Active Comparator: ARM 2 (SOC ISRT); Patients undergo standard of care (SOC) radiation therapy once daily (excluding weekends): 24 Gy in 12 treatment fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.	Other: Questionnaire Administration; Ancillary studies; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Endoscopic Procedure; Undergo endoscopy; Other Names: ES; Endoscopy; Endoscopic Examination; Radiation: Involved-site Radiation Therapy (12 Fractions); Undergo ISRT in 12 fractions; Other Names: ISRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade 2 or higher acute adverse events (AEs)	AEs will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Acute toxicity will be reported as a proportion calculated as the number of patients with acute toxicity divided by the total number of treatment patients. Treatment cycles are 5 days ±2 days (Arm 1) and 16 days ±2 days (Arm 2).	Up to 14 days after radiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression rate	Local control will be defined as the number of days from end of radiation treatment until first local recurrence within 24 months post radiation treatment. Treatment cycles are 5 days ±2 days (Arm 1) and 16 days ±2 days (Arm 2).	Up to 24 months after radiation treatment
Response rate	Response rate will be defined as the proportion of patients displaying response (complete response or partial response) at 3 months post treatment. Complete response is defined as the disappearance of all signs of cancer in response to treatment. Partial response is defined decrease in the size of target lesions by ≥ 50%, with no increase in the size of any lesion and no appearance of new lesions. Treated patients who do not have a 3-month evaluation will be classified as a non-response. Treatment cycles are 5 days ±2 days (Arm 1) and 16 days ±2 days (Arm 2).	Up to 3 months after radiation treatment
Patient reported quality of life	Patient reported quality of life will be measured using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, a 13-item questionnaire answered on a scale of 1-5 where 1=Not at all and 5=Very much. Treatment cycles are 5 days ±2 days (Arm 1) and 16 days ±2 days (Arm 2).	Up to 3 months after radiation treatment

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Brad S. Hoppe, MD, MPH, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Recurrence; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy; Endoscopy
• Other Study ID Numbers: MC230808 (Mayo Clinic); 23-010273 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No