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

Mayo Clinic

Status and phase: Enrolling; Phase 2

Conditions: Refractory Indolent B-Cell Non-Hodgkin Lymphoma; Recurrent Indolent B-Cell Non-Hodgkin Lymphoma; Recurrent Indolent Non-Hodgkin Lymphoma; Refractory Indolent Non-Hodgkin Lymphoma; Indolent B-Cell Non-Hodgkin Lymphoma

Treatments: Other: Questionnaire Administration; Radiation: Involved-site Radiation Therapy (3 Fractions); Procedure: Endoscopic Procedure; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Radiation: Involved-site Radiation Therapy (12 Fractions)

Study type: Interventional

Funder types: Other

Identifiers

NCT06386315

MC230808 (Other Identifier)

NCI-2024-03242 (Registry Identifier)

23-010273 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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112 participants in 2 patient groups

ARM 1 (reduced dose ISRT)

Experimental group

Description:

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.

Treatment:

Procedure: Positron Emission Tomography

Procedure: Computed Tomography

Procedure: Endoscopic Procedure

Radiation: Involved-site Radiation Therapy (3 Fractions)

Other: Questionnaire Administration

ARM 2 (SOC ISRT)

Active Comparator group

Description:

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.

Treatment:

Radiation: Involved-site Radiation Therapy (12 Fractions)

Procedure: Positron Emission Tomography

Procedure: Computed Tomography

Procedure: Endoscopic Procedure

Other: Questionnaire Administration