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Recurrent MelanomaPhase 2NCT02203604

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

A Phase 2 study testing aldesleukin, ipilimumab and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IIIA Melanoma, run by CINJRegulatory at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
aldesleukin, ipilimumab and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
6 sitesUnited States
Study dates
26 Nov 2014to 27 Jan 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37240

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Providence Portland Medical Center

    Portland, Oregon, 97213

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
aldesleukin, ipilimumab, laboratory biomarker analysis
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given IV

  • ipilimumabBiological

    Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02203604
Study groupRoleWhat they receive
Treatment (aldesleukin, ipilimumab)ExperimentalINDUCTION: 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.
Receives: Biological: aldesleukin; Biological: ipilimumab; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 24 weeks

Secondary outcomes (6)

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

    The number of participants with adverse in each classification of severity and relationship to treatment will be reported.

    Measured: Up to 60 weeks

  2. Overall Survival

    number of until death from any cause after the start of treatment

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

  3. Count of Participants With Increased Effector CD8+ T Cells

    Count of participants from the date of diagnosis or the start of treatment.

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

  4. Best Overall Response, Defined as the Best Response Across All Time Points

    Best overall response was defined as participants who achieved a complete or partial overall response as assessed by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions

    Measured: After the first 24 weeks

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

    Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% confidence intervals [CI]).

    The purity of the CD8+ T cells can then be measured via flow cytometry next the cells are counted and categorized.

    Measured: Up to 104 weeks

  6. Frequency of CD4+FoxP3+ Regulatory T Cells

    Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% CI).Using flow cytometry.

    Measured: Up to 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2014 (estimated)
  2. Study start26 Nov 2014
  3. Primary completion27 Jan 2020
  4. Study completion27 Jan 2020

Why it stopped: Insufficient rate of accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02203604
Sponsor's protocol ID
091309
Other IDs
NCI-2014-01306, CA184-084, Pro20140000135, P30CA072720, Pro20140000135
Status last verified
Jul 2023
First submitted
28 Jul 2014
Last updated
18 Jul 2023
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 31998643

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing aldesleukin, ipilimumab and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IIIA Melanoma, run by CINJRegulatory at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate as Determined by mWHO Criteria (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02203604, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2023.

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