High-Dose Aldesleukin and Ipilimumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed By Surgery

NCT02203604 | Terminated Phase 2 Results DMC

• 5 other identifiers: 091309NCI-2014-01306CA184-084Pro20140000135P30CA072720
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial studies how well high-dose aldesleukin and ipilimumab works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Biological therapies, such as aldesleukin, may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as ipilimumab, interfere with the ability of tumor cells to grow and spread. Giving high-dose aldesleukin together with ipilimumab may work better in treating patients with melanoma.

Conditions

Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate as Determined by mWHO Criteria

  Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.

  Up to 24 weeks

Secondary Outcomes (6)

• Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 60 weeks

• Overall Survival

  Time from the date of registration to the date of death from any cause, assessed up to 3 years

• Count of Participants With Increased Effector CD8+ T Cells

  Time from the date of registration until the date of documented disease progression or death, assessed up to up to 104 weeks

• Best Overall Response, Defined as the Best Response Across All Time Points

  After the first 24 weeks

• Count of Participants With Increased Effector CD8+ T Cells - Frequency of Effector CD8+ T Cells

  Up to 104 weeks

Study Arms (1)

Treatment (aldesleukin, ipilimumab)

EXPERIMENTAL

INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47. MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.

Biological: aldesleukin; Biological: ipilimumab; Other: laboratory biomarker analysis

Interventions

aldesleukin BIOLOGICAL

Given IV

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (aldesleukin, ipilimumab)

ipilimumab BIOLOGICAL

Given IV

Also known as: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

Treatment (aldesleukin, ipilimumab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (aldesleukin, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent
• Histologic or cytologic diagnosis of cutaneous melanoma that is considered unresectable (stage III) or metastatic (stage IV); ocular and mucosal melanoma is excluded
• White blood cell (WBC) \>= 2000/uL
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets \>= 75 x 10\^3/uL
• Hemoglobin \>= 9 g/dL (\>= 80 g/L; may be transfused)
• Creatinine =\< 2.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN for patients without liver metastasis, =\< 5 times for patients with liver metastases
• Bilirubin =\< 2.0 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• No known active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; testing is not required unless clinically suspected
• Performance status (Eastern Cooperative Oncology Group \[ECOG\] 0-1)
• Patients must have a life expectancy of greater than three months at the start of the trial
• Patients must have a brain magnetic resonance imaging (MRI) that is free of active metastases; metastases that have been treated with radiation or surgical resection, are stable for at least 4 weeks and do not require steroids are eligible
• Patients may have received treatment of completely resected early stage melanoma, comprising interferon, radiation treatment, or experimental vaccine therapy, and in the metastatic setting patient can have had treatment such as chemotherapy, immunotherapy (except prior treatment with ipilimumab and IL-2), and other experimental agent which was completed 4 weeks prior to enrollment
• Normal cardiac stress test for patients over 50 years of age

You may not qualify if:

• Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
• Patients with primary ocular or mucosal melanoma are excluded
• Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and Myasthenia Gravis)
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
• Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult; patients with reversible ischemic changes on cardiac stress test
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
• A history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte antigen 4 (CTLA4) inhibitor or agonist
• Concomitant therapy with any of the following: interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids
• Women of childbearing potential (WOCBP), who:
• Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
• Have a positive pregnancy test at baseline, or
• Are pregnant or breastfeeding
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness

Sponsors & Collaborators

• CINJRegulatory: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (6)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37240, United States

Location

Related Publications (1)

• Silk AW, Kaufman HL, Curti B, Mehnert JM, Margolin K, McDermott D, Clark J, Newman J, Bommareddy PK, Denzin L, Najmi S, Haider A, Shih W, Kane MP, Zloza A. High-Dose Ipilimumab and High-Dose Interleukin-2 for Patients With Advanced Melanoma. Front Oncol. 2020 Jan 10;9:1483. doi: 10.3389/fonc.2019.01483. eCollection 2019.

  PMID: 31998643 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Interleukin-2; Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; 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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biomarkers

Limitations and Caveats

The trial was closed early due to slow accrual. Early termination lead to a small number of subjects analyzed.

Results Point of Contact

• Title: Ann Silk, MD
• Organization: Dana Farber Cancer Institute

Ann_Silk@dfci.harvard.edu

617-632-6571

Study Officials

• Howard Kaufman

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CINJ Clinical Trial Administrator

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: July 30, 2014
• Study Start: November 26, 2014
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: July 18, 2023
• Results First Posted: June 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)