MC230808 Reduced Dose Hypofractionated Radiotherapy (3Gy x 3 Fractions) for Indolent Non-Hodgkin Lymphoma (POSEIDON): A Multisite Phase 2 Randomized Trial
Overview
- Phase
- Phase 2
- Intervention
- Computed Tomography
- Conditions
- Indolent B-Cell Non-Hodgkin Lymphoma
- Sponsor
- Mayo Clinic
- Enrollment
- 112
- Locations
- 14
- Primary Endpoint
- Incidence of grade 2 or higher acute adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 10 days ago
Overview
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 \[9 gray (Gy) in 3 fractions, 8 Gy in 2 fractions, or 10 Gy in 5 fractions\] 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.
Investigators
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
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
Arms & Interventions
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.
Intervention: Computed Tomography
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.
Intervention: Endoscopic Procedure
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.
Intervention: Involved-site Radiation Therapy (3 Fractions)
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.
Intervention: Positron Emission Tomography
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.
Intervention: Questionnaire Administration
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.
Intervention: Computed Tomography
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.
Intervention: Endoscopic Procedure
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.
Intervention: Involved-site Radiation Therapy (12 Fractions)
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.
Intervention: Positron Emission Tomography
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.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Incidence of grade 2 or higher acute adverse events (AEs)
Time Frame: Up to 14 days after radiation treatment
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).
Secondary Outcomes
- Response rate(Up to 3 months after radiation treatment)
- Time to progression rate(Up to 24 months after radiation treatment)
- Patient reported quality of life(Up to 3 months after radiation treatment)