Radiation Therapy Plus Durvalumab for Tumor-Stage Cutaneous T-Cell Lymphoma

Study Overview
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Brief Summary
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This is a single arm, single stage pilot study of radiation therapy plus durvalumab for tumor-stage cutaneous T-cell lymphoma (CTCL).

Official Title
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A Single Arm Pilot Study of Radiation Therapy Plus Durvalumab for Tumor-Stage Cutaneous T-Cell Lymphoma

Conditions
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Cutaneous T Cell Lymphoma

Intervention / Treatment
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* Drug: Durvalumab
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily provide written IRB-approved consent Age ≥ 18 years Histologically proven CTCL Stage IIB-IV CTCL with ≥2 cutaneous tumors assessable for response At least one cutaneous tumor amenable to radiation therapy. Must have at least 1 tumor assessable for response that will not undergo radiation. Adequate organ function Prior treatment is allowed if at least 4 weeks have elapsed since last chemotherapy and/or radiation and the subject has recovered from all treatment related toxicity Exclusion Criteria: Prior allogeneic stem cell transplant. Prior treatment with a PD-1/PD-L1 inhibitor Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment. Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab. Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection. History of hypersensitivity to durvalumab or any excipient Receipt of live attenuated vaccination within 30 days prior the first dose of durvalumab. Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control Male subjects who are not employing an effective method of birth control Uncontrolled current medical illness, including, but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris,unstable cardiac arrhythmia and/or psychiatric illness or other condition that in the opinion of the investigator would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy + Durvalumab<br>Radiation to 1-3 cutaneous tumors: 20 Gy (4 Gy x 5 fractions) Durvalumab 1500mg IV over 1 hour administered within 2-7 days of initiation of radiation, then every 28 days. | Drug: Durvalumab<br>* Durvalumab 1500mg IV over 1 hour administered within 2-7 days of initiation of radiation, then every 28 days.<br>Radiation: Radiation Therapy<br>* Radiation to 1-3 cutaneous tumors: 20 Gy (4 Gy x 5 fractions)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients that respond to treatment | Overall Response Rate (ORR) is defined as the percentage of patients that obtain a Complete Response (CR) or Partial Response (PR) to treatment. A global composite scoring system will be used to determine response. Skin, nodes, viscera and blood will be assessed. | 1 year post treatment | 
| The percentage of patients that completely respond to treatment | Complete Response Rate (CRR) is defined as the percentage of patients that obtain Complete Response (CR) to treatment. A global composite scoring system will be used to determine response. Skin, nodes, viscera and blood will be assessed. | 1 year post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | The time to response is measured from the start of the treatment until criteria are met for CR or PR. A global composite scoring system will be used to determine response. Skin, nodes, viscera and blood will be assessed. | 1 year post treatment | 
| Duration of overall response | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrence or PD (Progressive disease) is objectively documented. A global composite scoring system will be used to determine response and progression. Skin, nodes, viscera and blood will be assessed. | 1 year post treatment | 
| Progression free survival time | Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. A global composite scoring system will be used to determine progression. Skin, nodes, viscera and blood will be assessed. | 1 year post treatment | 
| Time to next treatment | Time to next treatment is defined as the duration of time from start of study treatment to next treatment or death of any cause, whichever comes first. | 1 year post treatment |