Lymphoma RadVax LYMPHOMA: A PHASE II TRIAL OF NIVOLUMAB + LOW DOSE RADIOTHERAPY FOR INCOMPLETE RESPONDERS

Study Overview
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Brief Summary
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This is a Phase II single-arm, single-site, open label clinical trial with r/r HL patients, aimed to determine whether a RadVax approach using low-dose RT added to nivolumab can improve response among patients who do not achieve a CR to nivolumab alone. The long-term goal is to develop an effective regimen for r/r HL patients.

Detailed Description
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Nivolumab 3 mg/kg will be administered on day 1 (pre-response assessment week 0) and on day 1 and continued per standard of care and institutional practices. At the week 1 biomarker collection, research FDG PET/CT will be performed to assess for FDG flare. At week 8-12, PET/CT will be performed for the first response assessment. If a complete anatomic response is seen, nivolumab monotherapy will be continued on day 1 and continued per standard of care and institutional practices. By contrast, if at week 8 less than a complete anatomic response is seen, radiotherapy to 4 Gy x 2 fractions will be administered (post-response assessment week 0). The patient will be evaluated by a radiation oncologist while on treatment, and toxicities will be recorded. Nivolumab will be continued on day 1 and continued per standard of care and institutional practices. In either scenario, a second response assessment will be conducted  8-12 weeks after the first response assessment. In either scenario, nivolumab monotherapy will be continued at the discretion of the treating medical oncologist. If there is less than CR post-RT and there is an additional untreated non-target lesion that can be followed, radiotherapy can again be administered when disease progresses to a previously untreated lesion, after which the patient will continue on the post-RT follow-up algorithm.

Official Title
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RadVax for Relapsed/Refractory Hodgkin's Lymphoma: A Phase II Trial of Nivolumab + Low Dose Radiotherapy for Incomplete Responders

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed Hodgkin lymphoma for whom nivolumab is clinically indicated. Relapsed/refractory disease. ≥2 sites of measurable disease, at least one outside of intended RT fields. Age ≥ 18 years. ECOG performance status of 0-2. Standard laboratory criteria for hematologic, and biochemical, and urinary indices within a range that, in the opinion of the physician, clinically supports enrollment of the subject on the trial. Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial. Ability to provide written informed consent. Exclusion Criteria: Subjects with contraindications to immune checkpoint therapy, as follows: Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. Prior organ allograft or allogeneic bone marrow transplantation. Subjects with contraindications to immune checkpoint therapy, as follows: Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. Prior organ allograft or allogeneic bone marrow transplantation. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator. Condition requiring systemic treatment with either corticosteroids. Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are strongly discouraged Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted. Pregnant women, women planning to become pregnant and women that are nursing.

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: Single Arm<br>Subjects will receive initial treatment with the immunomodulatory agent, nivolumab, followed by low-dose (4 Gy x 2) involved-site radiotherapy in subjects with less than an anatomic CR after the first restaging scan. Patients with anatomic CR will continue nivolumab alone without radiotherapy. Eligible patients will have r/r disease with at least 2 sites of measurable disease, and must be eligible for treatment with nivolumab. | Drug: Nivolumab<br>* Nivolumab 3 mg/kg will be administered on day 1 (pre-response assessment week 0) and on day 1 and continued per standard of care and institutional practices. A<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Overall complete response rate as determined by re-staging scan | 25 weeks |