Ultra Low Dose Orbital Radiation Therapy in Treating Patients With Stage I-IV Indolent B-cell Lymphoma or Mantle Cell Lymphoma

Phase 2

Active, not recruiting

• Conditions: Ann Arbor Stage I B-Cell Non-Hodgkin Lymphoma; Ann Arbor Stage I Grade 1 Follicular Lymphoma; Ann Arbor Stage I Grade 2 Follicular Lymphoma; Ann Arbor Stage I Indolent Adult Non-Hodgkin Lymphoma; Ann Arbor Stage III Mantle Cell Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Mantle Cell Lymphoma; Ann Arbor Stage I Mantle Cell Lymphoma; Ann Arbor Stage II Grade 1 Follicular Lymphoma; Ann Arbor Stage II B-Cell Non-Hodgkin Lymphoma
• Interventions: Radiation: External Beam Radiation Therapy; Drug: Orbital Radiation

• Registration Number: NCT02494700
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase II trial studies how well ultra low dose orbital radiation therapy works in treating patients with stage I-IV low grade (indolent) B-cell lymphoma or mantle cell lymphoma involving the orbit of the eye (space enclosed by the borders of the eye socket). Orbital radiation therapy uses external beam radiation to destroy cancer cells. Using ultra low dose orbital radiation therapy may be effective in treating indolent B-cell lymphoma or mantle cell lymphoma involving the eye and may have fewer side effects.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of ultra low dose 4 Gray (Gy) orbital radiation, measured as local orbital control (i.e. local control within the radiation field), in patients with limited and advanced stage low grade B lymphocyte (B cell) lymphoma and mantle cell lymphoma involving the ocular adnexa.

II. To evaluate the efficacy of ultra low dose 4 Gy orbital radiation, measured as complete response, in patients with limited and advanced stage low grade B cell lymphoma and mantle cell lymphoma involving the ocular adnexa.

III. To evaluate the acute and chronic toxicity of radiation to the orbit.

SECONDARY OBJECTIVE:

I. To determine if dynamic contrast enhanced magnetic resonance imaging can predict response to ultra low dose radiation therapy.

OUTLINE:

Patients undergo low dose orbital external beam radiation therapy (EBRT) on 2 consecutive days. Patients experiencing stable or progressive disease after 12-16 weeks of EBRT undergo additional low dose orbital EBRT over 10 fractions. Patients experiencing partial response or minimal response 1 year after EBRT also undergo low dose orbital EBRT over 10 fractions.

After completion of study treatment, patients are followed up every 3-4 months for 6-8 months, every 6-12 months for up to 2 years, and then periodically thereafter.

Study Timeline

• Study Start: 2015-07-06
• Study First Submitted: 2015-07-08
• Study First Submitted QC: 2015-07-09
• Study First Posted: 2015-07-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-16
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients 18 years or older with stage I-IV indolent B cell lymphoma, including MALT and follicular grade I/II. Patients with mantle cell lymphoma will also be included in this study, as mantle cell lymphoma is also radiosensitive, despite it not being an indolent B cell lymphoma. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are ineligible.
• Patients must have measurable disease within the orbit, either clinically and/or radiographically after biopsy confirmation of B cell lymphoma.
• Bilateral ocular adnexal involvement is permitted, if biopsy confirms unilateral disease and there is high clinical suspicion for bilateral disease, biopsy of the contralateral ocular adnexa can be waived.
• Female patients of childbearing potential must have a negative serum pregnancy test (βhCG) within 2 weeks of protocol entry.
• Planned systemic therapy after orbital radiation therapy is permitted however the timing of systemic therapy will be recorded and patients will be stratified according to receipt of adjuvant systemic therapy.
• Male patients must agree to use a barrier method of contraception or agree to abstain from heterosexual activity for the duration of the study.
• Female patients must be willing to use two adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study or be post-menopausal (free from menses > two years or surgically sterilized).
• Patients must have the ability to give informed consent.

Exclusion Criteria

• Patients treated with chemotherapy for lymphoma within 4 weeks of protocol enrollment (including Rituxan).
• Patients with aggressive B cell lymphoma histology, including diffuse large B cell lymphoma (DLBCL) and grade 3 follicular lymphoma.
• Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
• Patients with a history of prior radiation to the orbit if re-treatment would exceed known orbital tolerance.
• Patients with pre-existing retinopathy.
• Patients who are pregnant.
• Patients with active lupus or scleroderma are ineligible

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (low dose orbital EBRT)	External Beam Radiation Therapy	Patients undergo two fractions of low dose orbital EBRT on 2 consecutive days. Patients experiencing stable or progressive disease after 12-16 weeks of EBRT undergo additional low dose orbital EBRT over 10 fractions. Patients experiencing partial response or minimal response 1 year after EBRT also undergo low dose orbital EBRT over 10 fractions.
Treatment (low dose orbital EBRT)	Orbital Radiation	Patients undergo two fractions of low dose orbital EBRT on 2 consecutive days. Patients experiencing stable or progressive disease after 12-16 weeks of EBRT undergo additional low dose orbital EBRT over 10 fractions. Patients experiencing partial response or minimal response 1 year after EBRT also undergo low dose orbital EBRT over 10 fractions.

Primary Outcome Measures

Name	Time	Method
Local orbital control (i.e. local control within the radiation field)	Up to 2 years post-radiation	Local orbital event will be estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Freedom from distant relapse rates	Up to 2 years
Complete response rate	Up to 2 years	Response rate will be estimated along with 95% confidence intervals.
Local regional control (i.e. local control within the ipsilateral orbit but outside of the radiation field)	Up to 2 years post-radiation therapy
Overall survival (OS)	Up to 2 years	OS will be estimated using the Kaplan-Meier method.
Incidence of acute and chronic ocular toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03	Up to 2 years	Toxicity data will be summarized by frequency tables.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States