Clinical trial NCT03495713: Lymphoma RadVax LYMPHOMA: A PHASE II TRIAL OF NIVOLUMAB + LOW DOSE RADIOTHERAPY FOR INCOMPLETE RESPONDERS
Official title: RadVax for Relapsed/Refractory Hodgkin's Lymphoma: A Phase II Trial of Nivolumab + Low Dose Radiotherapy for Incomplete Responders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2018-04-12
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Response Rate
timeFrame: 25 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: John Plastaras, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: