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.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Nivolumab | Opdivo | Single Arm |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Single Arm | Experimental | 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. |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Complete response rate |
| Time Frame: | 25 weeks |
| Safety Issue: | |
| Description: | Overall complete response rate as determined by re-staging scan |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Abramson Cancer Center of the University of Pennsylvania |
April 12, 2021
