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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04562129
Recruitment Status : Recruiting
First Posted : September 24, 2020
Last Update Posted : September 25, 2020
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease Intervention/treatment Phase
Melanoma Stage III Melanoma Stage IV Inoperable Disease Drug: Interleukin-2 Drug: Ipilimumab Drug: Nivolumab Phase 2

Detailed Description:

This is a Phase II study of high dose bolus interleukin-2 (HD IL2) in combination with low dose ipilimumab followed sequentially by nivolumab in patients with advanced inoperable stage III or stage IV melanoma who have failed prior anti-PD1 immunotherapy.

The planned treatment consists of 3 courses (One cycle is 21 days and one course is 4 cycles). HD IL2 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 on Day 1 of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on Day 1 of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Response assessment will occur at the end of 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of High Dose Bolus IL2 in Combination With Low Dose Ipilimumab Followed Sequentially by Nivolumab in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2029

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Treatment
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 on Day 1 of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on Day 1 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
High dose interleukin-2 (HD IL2) administered week 1 and 4 of each course (approximately 12 weeks)
Other Name: Aldesleukin

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

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

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 9 months ]
    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.

Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 5 years ]
    Progression Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression (or death if there is no progression date). Patients with neither a progression date nor date of death will be censored as of last contact.

  2. Overall Survival [ Time Frame: Up to 5 years ]
    Overall Survival (OS) will be measured from the initial date of treatment to the recorded date of death.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • 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, within 3 months of registration on this study.
  • Must not have received systemic therapy or radiotherapy 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 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 with BRAF V600 mutant melanoma must have previously received BRAF targeted therapy for metastatic melanoma and later experienced disease progression. Patients who refuse 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.
  • Patients who are over 40 years old or have had previous myocardial infarction greater than 6 months prior to study entry or have significant cardiac family history (CAD or serious arrhythmias) will be required to have a negative or low probability cardiac stress test (for example, thallium stress test, stress multigated acquisition scan (MUGA), stress echo or exercise stress test) for cardiac ischemia within 8 weeks prior to registration.
  • No history of cerebrovascular accident or transient ischemic attacks within the past 6 months from registration.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Women should not be lactating and, if of childbearing age, should have a negative pregnancy test (b-HCG test; serum or urine, minimum sensitivity 25 IU/L or equivalent units of b-HCG) within two weeks of registration in the study.

Exclusion Criteria:

  • 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, adrenal insufficiency, hypopituitarism) are eligible if they are stable on hormone replacement therapy.
  • Patients may not be receiving any other investigational agents.
  • Patients with active brain metastasis are excluded
  • Patients with clinically significant cardiovascular or cerebrovascular disease
  • PT INR >1.5 unless the patient is on full-dose warfarin.
  • 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. Patients stable on physiologic replacement doses of steroids or other forms of hormone replacement therapy are eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04562129

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Contact: Lori McCormick 813-745-4858

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United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Lori McCormick    813-745-4858   
Principal Investigator: Ahmad Tarhini, MD, PhD         
Sub-Investigator: Andrew Brohl, MD         
Sub-Investigator: Zeynep Eroglu, MD         
Sub-Investigator: Nikhil Khushalani, MD         
Sub-Investigator: Joseph Markowitz, MD, PhD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
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Principal Investigator: Ahmad Tarhini, MD, PhD Moffitt Cancer Center
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT04562129    
Other Study ID Numbers: MCC-20494
CIIT19PLK13 ( Other Identifier: Clinigen )
First Posted: September 24, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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.: Yes
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
skin cancer
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents