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

Information source: Rutgers, The State University of New Jersey
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

Intervention: aldesleukin (Biological); ipilimumab (Biological); laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: Rutgers, The State University of New Jersey

Official(s) and/or principal investigator(s):
Howard Kaufman, Principal Investigator, Affiliation: Rutgers Cancer Institute of New Jersey

Overall contact:
Clinical Trials Office, Phone: 732-235-8675


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.

Clinical Details

Official title: A Phase II Single Arm Study of High-Dose IL-2 and Ipilimumab in Patients With Unresectable Stage III and Stage IV Melanoma

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Objective response rate as determined by mWHO criteria

Secondary outcome:

Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Overall survival

PFS based on the mWHO criteria

BOR, defined as the best response across all time points

Frequency of effector CD8+ T cells

Frequency of CD4+FoxP3+ regulatory T cells

Detailed description: PRIMARY OBJECTIVES: I. The best overall response rate within the first 24 weeks of combination interleukin (IL)-2 (aldesleukin) and ipilimumab using the immune-related response criteria. SECONDARY OBJECTIVES: I. Best overall response (BOR). II. Progression-free survival (PFS). III. Disease control rate (DCR). IV. Overall survival. V. To collect data on the safety and feasibility of combined high-dose IL-2 and ipilimumab. VI. To evaluate the cluster of differentiation (CD)4+ and CD8+ T cell response in the tumor microenvironment and peripheral blood of patients treated on this study. OUTLINE: INDUCTION: Patients receive ipilimumab intravenously (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. After completion of study treatment, patients are followed up every 3 months for 36 months.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- 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


- 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

- Forced expiratory volume in 1 second (FEV1) > 65% of prediction for those patients

with extensive pulmonary metastases or chronic pulmonary disease history

- Forced vital capacity (FVC) > 65% of prediction for those patients with extensive

pulmonary metastases or chronic pulmonary disease history

- Women of childbearing potential (WOCBP) must be using an adequate method of

contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; in general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as:

- Amenorrhea >= 12 consecutive months without another cause, or

- For women with irregular menstrual periods and taking hormone replacement

therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL

- Women who are using oral contraceptives, other hormonal contraceptives (vaginal

products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25

IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours before the start of ipilimumab

- Men of fathering potential must be using an adequate method of contraception to

avoid conception throughout the study (and for up to 26 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized Exclusion Criteria:

- 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

Locations and Contacts

Clinical Trials Office, Phone: 732-235-8675

Loyola University Medical Center, Maywood, Illinois 60153, United States; Not yet recruiting
Joseph I. Clark, Phone: 708-226-4357
Joseph I. Clark, Principal Investigator

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Not yet recruiting
David F. McDermott, Phone: 617-667-9925
David F. McDermott, Principal Investigator

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Not yet recruiting
Marc S. Ernstoff, Phone: 603-650-7609, Email: cancerhelp@dartmouth.edu
Marc S. Ernstoff, Principal Investigator

Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, United States; Recruiting
Clinical Trials Office, Phone: 732-235-8675
Howard L. Kaufman, Principal Investigator

Providence Portland Medical Center, Portland, Oregon 97213, United States; Recruiting
Brendan D. Curti, Phone: 503-215-6412
Brendan D. Curti, Principal Investigator

Vanderbilt University Medical Center, Nashville, Tennessee 37240, United States; Not yet recruiting
Jeffrey A. Sosman, Phone: 800-811-8480
Jeffrey A. Sosman, Principal Investigator

Additional Information

Starting date: November 2014
Last updated: March 18, 2015

Page last updated: August 23, 2015

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