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

• ClinicalTrials.gov Identifier: NCT03495713
• Recruitment Status: Terminated
• First Posted: April 12, 2018
• Last Update Posted: May 23, 2022
• Sponsor: Abramson Cancer Center at Penn Medicine
• Information provided by (Responsible Party): Abramson Cancer Center at Penn Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hodgkin Lymphoma	Drug: Nivolumab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RadVax for Relapsed/Refractory Hodgkin's Lymphoma: A Phase II Trial of Nivolumab + Low Dose Radiotherapy for Incomplete Responders
• Actual Study Start Date: March 2, 2018
• Actual Primary Completion Date: April 20, 2022
• Actual Study Completion Date: April 20, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single Arm; 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; 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; Other Name: Opdivo

Outcome Measures

Primary Outcome Measures :

1. Complete response rate [ Time Frame: 25 weeks ]
   Overall complete response rate as determined by re-staging scan

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Pennsylvania

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19035

Sponsors and Collaborators

Abramson Cancer Center at Penn Medicine

Investigators

• Principal Investigator: John Plastaras, MD, PhD; Abramson Cancer Center at Penn Medicine

More Information

• Responsible Party: Abramson Cancer Center at Penn Medicine
• ClinicalTrials.gov Identifier: NCT03495713
• Other Study ID Numbers: UPCC 04418
• First Posted: April 12, 2018
• Last Update Posted: May 23, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action