IL2 With Ipilimumab Followed by Nivolumab in Stage 3 or 4 Melanoma Patients

NCT04562129 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-20494CIIT19PLK13
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.

Conditions

Melanoma Stage III; Melanoma Stage IV; Inoperable Disease

Keywords

skin cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response rate (Complete Response + Partial Response) of HD IL2 plus low dose ipilimumab followed sequentially by nivolumab in patients with inoperable stage III or stage IV melanoma who have either failed prior treatment with anti-PD1 immunotherapy (nivolumab or pembrolizumab) or have demonstrated tumor progression following such therapy.

  Up to 9 months

Secondary Outcomes (2)

• Progression Free Survival

  Up to 5 years

• Overall Survival

  Up to 5 years

Study Arms (1)

Treatment

EXPERIMENTAL

HD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg during week one of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on during week one of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.

Drug: Interleukin-2; Drug: Ipilimumab; Drug: Nivolumab

Interventions

Interleukin-2 DRUG

High dose interleukin-2 (HD IL2) administered week 1 and 4 of each course (approximately 12 weeks)

Also known as: Aldesleukin

Treatment

Ipilimumab DRUG

Low dose Ipilimumab given at time of HD IL2 administration on day 1 of the first 2 cycles of each course.

Treatment

Nivolumab DRUG

Nivolumab will be given at a dose of 480 mg IV week 7 of each course.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic melanoma. This includes American Joint Committee on Cancer (AJCC) stage IV or advanced/inoperable stage III. This also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases
• Measurable disease, according to RECIST version 1.1
• Must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
• Must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and later experienced disease progression.
• Must not have received systemic therapy or radiotherapy (including SRS) within the preceding 3 weeks. Patients must have recovered from adverse events from previous therapy by the time registration.
• Must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery, and must be free of significant detectable infection prior to registration.
• Patients who have received prior anti-CTLA4 monoclonal antibody therapy (ipilimumab or tremelimumab) are eligible.
• Patients who have previously experienced prior high-grade (grade 3 or 4 by CTCAE criteria) immune related adverse events with immune checkpoint inhibitors must be discussed with the study PI and cleared prior to enrollment on this study in order to ensure patient safety.
• Patients with BRAF V600 mutant melanoma must have previously received BRAF targeted therapy for metastatic melanoma and later experienced disease progression. Patients who refuse or decline to receive BRAF targeted therapy or were intolerant of BRAF targeted therapy are eligible.
• Life expectancy of greater than 3 months in the opinion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Must have normal organ and marrow function as specified per protocol.
• Patients on full-dose anticoagulants with Prothrombin Time Test International Normalized Ratio (PT INR) \>1.5 are eligible provided that both of the following criteria are met: (a) The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. (b) The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
• Pulmonary: Forced Expiratory Volume at 1 second (FEV1) \> 2.0 liters or \> 75% of predicted for height and age. Pulmonary function tests (PFTs) are required for patients over 50 years old or with significant pulmonary or smoking history
• No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina.

You may not qualify if:

• Patients who have had systemic therapy for melanoma or radiotherapy within 3 weeks prior to registering on the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Patients with a history of endocrinopathies (e.g. hypothyroidism) are eligible if they are stable on hormone replacement therapy. Patients with a history of adrenal insufficiency are not eligible.
• Patients may not be receiving any other investigational agents.
• Patients with active brain metastasis are excluded
• Patients with clinically significant cardiovascular or cerebrovascular disease
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for \> 2 years prior to the time of registration. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
• Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids or steroid inhalers. If a patient had been taking steroids, at least 2 weeks must have passed since the last dose.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Clinigen, Inc.: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Clinical Trials Website

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Interleukin-2; aldesleukin; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Ahmad Tarhini, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnay Marshall

CONTACT

813-745-5938; Arnay.Marshall@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 24, 2020
• Study Start: September 24, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)