Clinical trial NCT06386315: Reduced Dose Radiotherapy for the Treatment of Indolent Non-Hodgkin Lymphoma
Official title: Reduced Dose Hypofractionated Radiotherapy (3Gy x 3 Fractions) for Indolent Non-Hodgkin Lymphoma (POSEIDON): A Multisite Phase 2 Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Indolent B-Cell Non-Hodgkin Lymphoma
Recurrent Indolent B-Cell Non-Hodgkin Lymphoma
Refractory Indolent B-Cell Non-Hodgkin Lymphoma
Recurrent Indolent Non-Hodgkin Lymphoma
Refractory Indolent Non-Hodgkin Lymphoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2024-04-26
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: PRIMARY OBJECTIVE:

I. To show that the experimental arm (9 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, 3 months then every 6 months for up to 2 years.

Eligibility criteria: 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 (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
  * Men or women of childbearing potential who are unwilling to employ adequate contraception
* T-cell lymphoma
* Small and chronic lymphocytic lymphoma
* Grade 3B follicular lymphoma

Primary outcomes:
measure: Incidence of grade 2 or higher acute adverse events (AEs)
timeFrame: Up to 14 days after radiation treatment
Secondary outcomes:
measure: Response rate
timeFrame: Up to 3 months after radiation treatment
measure: Time to progression rate
timeFrame: Up to 24 months after radiation treatment
measure: Patient reported quality of life
timeFrame: Up to 3 months after radiation treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Albert Lea
country: United States
facility: Mayo Clinic Health System in Albert Lea
state: Minnesota
city: Mankato
country: United States
facility: Mayo Clinic Health System - Mankato
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Eau Claire
country: United States
facility: Mayo Clinic Health System-Eau Claire Clinic
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System-Franciscan Healthcare
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Bradford S. Hoppe, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: