- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00726739
Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma
A Randomized Phase II Study of IL-2 With or Without an Allogeneic Large Multivalent Immunogen (LMI) Vaccine for the Treatment of Stage IV Melanoma
RATIONALE: Aldesleukin may stimulate the white blood cells to kill tumor cells. Vaccines may help the body build an effective immune response to kill tumor cells. Giving aldesleukin together with vaccine therapy may kill more tumor cells. It is not yet known whether aldesleukin is more effective with or without vaccine therapy in treating melanoma.
PURPOSE: This randomized phase II trial is studying how well aldesleukin works when given with or without vaccine therapy in treating patients with stage IV melanoma.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
OBJECTIVES:
Primary
- To compare the progression-free survival of patients with stage IV melanoma treated with aldesleukin with vs without allogeneic large multivalent immunogen melanoma vaccine LP2307.
Secondary
- To compare the clinical response in patients treated with these regimens.
- To compare the 1- and 2-year survival rates in patients treated with these regimens.
- To determine whether an immune response is generated after vaccination in these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive allogeneic large multivalent immunogen melanoma vaccine LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (control): Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on arm I.
Patients undergo blood sample collection periodically for correlative laboratory studies. Samples are analyzed for immune responses to keyhole limpet hemocyanin and tetanus toxoid (control antigens) by ELISA assay; IFN-γ production by CD8 T cells in response to melanoma-derived peptides by ELISpot assay; delayed-type hypersensitivity response to vaccination; and frequency of peripheral blood lymphocytes, including T cells, B cells, NK cells, and monocytes, by flow cytometry.
- Arm III Crossover: Patients who have progressive disease on Arm II will be offered crossover to Arm I provided they continue to meet all study criteria.
After completion of study treatment, patients are followed every 2 months for 1 year, every 3 months until disease progression, and then periodically thereafter.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
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Minnesota
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Minneapolis, Minnesota, Stati Uniti, 55455
- Masonic Cancer Center, University of Minnesota
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Stage IV melanoma.
- Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed if at least 4 weeks since last treatment. Patient must recover from the acute toxic effects of the treatment prior to study enrollment.
- Disease status must be that of measurable or nonmeasurable disease as defined by Solid Tumor Response Criteria (RECIST)
- Karnofsky performance status >70% (Eastern Cooperative Oncology Group 0-1)
- Age 18 years or older
Adequate organ function within 14 days of study enrollment including the following:
- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 10^9/L, platelets ≥100 x 10^9/L, and hemoglobin ≥ 10 g/dL
- Hepatic: bilirubin < 3 times the upper limit of normal (× ULN), aspartate transaminase (AST) < 3 × ULN
- Renal: creatinine ≤ 2.0
- Must share at least one class I HLA allele with the HLA-type SK23-CD80+ cell (class I alleles (A1, A2, B7, B8, C7))
- Meets eligibility criteria for and agrees to enroll in "MT1999- 06: Vaccination with Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune Responses" (IRB # 9904M01581, CPRC #2002LS032)
- Women of childbearing potential and men whose partners are of childbearing potential are required to use an effective method of contraception (ie, a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after the last dose of study drug.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Exclusion criteria:
- History of brain metastases or positive brain scan at on-study
- Immunosuppressive therapy i.e., prednisone or organ transplant patients, however topical or inhalational steroids are allowed.
- Autoimmune diseases requiring immunosuppressive therapy.
- History of symptomatic pulmonary disease will have pulmonary function tests (PFTs) performed. Patients with symptoms of dyspnea or rales, wheezes or rhonchi on physical exam will undergo PFTs. Those with FEV1 <50% of predicted or corrected DLCO <50% are not eligible.
- Patients with cardiac disease such as recent myocardial infarction (< 3 months prior), unstable angina, or heart failure requiring medical intervention will undergo cardiac evaluation. Cardiac testing may include ECG, MUGA or echocardiogram, and/or thallium stress test as indicated to evaluate cardiac risks. Those patients with exercise-induced ischemia or an ejection fraction by MUGA or echocardiogram < 40% are not eligible.
- Due to the origin of the KLH protein, patients with a history of seafood allergy are excluded from receiving KLH.
- Hypersensitivity to any component of the vaccine, including Thimerosal, a mercury derivative, is a contraindication (taken from tetanus toxoid package insert).
- The occurrence of any type of neurologic symptoms to tetanus vaccine in the past is a contraindication to further use (taken from tetanus toxoid package insert).
- Subjects who have had tetanus toxoid within the last 7 years will not receive the tetanus vaccine component of this
- Pregnant (positive pregnancy test) or lactating women. Use of LMI vaccine during pregnancy is not approved for use by the FDA during pregnancy. IL-2 is pregnancy category C - risk in pregnancy cannot be ruled out.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Arm I - LMI + aldesleukin
Patients receive allogeneic large multivalent immunogen vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
|
IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
Altri nomi:
Allogeneic tumor cell membrane-coated large multivalent immunogen (LMI [1 x 10^7, 5-μm silica spheres]) will be given as an intradermal injection every 4 weeks for up to 12 injections.
Each vaccine dose will be 0.2 ml.
Altri nomi:
|
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Comparatore attivo: Arm II (control) - aldesleukin
Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Patients with disease progression may cross over and receive treatment on arm I.
|
IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
Altri nomi:
|
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Sperimentale: Arm III - Crossover Patients
Patients who have progressive disease on Arm II were be offered crossover to Arm I provided they continued to meet all study criteria. Patients receive allogeneic large multivalent immunogen vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity |
IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
Altri nomi:
Allogeneic tumor cell membrane-coated large multivalent immunogen (LMI [1 x 10^7, 5-μm silica spheres]) will be given as an intradermal injection every 4 weeks for up to 12 injections.
Each vaccine dose will be 0.2 ml.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Median Time of Progression-free Survival
Lasso di tempo: From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.
|
Progression free survival (PFS) was measured in months from date of randomization to date of disease progression, or date of death.
For patients who died without tumor progression, PFS assumes their deaths are randomly related to tumor progression.
Therefore, PFS includes deaths if they came first.
|
From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Clinical Response of Lesion(s)
Lasso di tempo: Month 2 through Month 12
|
Beginning at 2 months Through End of Treatment: To determine clinical response of each treatment group - Best Clinical response will be determined using Solid Tumor Response Criteria (RECIST).
Complete Response (CR) = complete disappearance of all target lesions.
Partial Response (PR) = At least a 30% decrease in sum of longest diameters of target lesions.
Progressive Disease (PD) = At least a 20% increase in sum of longest diameters of target lesions.
Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR or PD.
|
Month 2 through Month 12
|
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Overall Survival at 2 Years
Lasso di tempo: 2 Years
|
Two year survival (alive at 2 years from randomization) rate of each treatment group.
|
2 Years
|
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Overall Survival at 1 Year
Lasso di tempo: 1 Year
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One year survival (alive at 1 year from randomization) rate of each treatment group.
|
1 Year
|
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Immune Response
Lasso di tempo: 48 hours After Study Medication
|
Immune responses is be assessed by Delayed Type Hypersensitive (DTH) responses to LMI, IFN-γ production by CD8 T cells using the ELISPOT assay, and CD8 T cell binding to HLA-A2 multimers complexed with melanoma-derived peptides (pentamer analysis).
DTH reactions are determined at 48 hours by measuring the largest diameter and right angle diameter of the area of induration and calculating the mean.
DTH responses are recorded as present or absent but cannot be used as a quantitative measure of immune activation.
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48 hours After Study Medication
|
Collaboratori e investigatori
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Tumori neuroectodermici
- Neoplasie, cellule germinali ed embrionali
- Neoplasie, tessuto nervoso
- Tumori neuroendocrini
- Nevi e melanomi
- Melanoma
- Effetti fisiologici delle droghe
- Agenti antinfettivi
- Agenti del sistema nervoso periferico
- Agenti antivirali
- Agenti anti-HIV
- Agenti antiretrovirali
- Analgesici
- Agenti del sistema sensoriale
- Analgesici, non narcotici
- Agenti antineoplastici
- Fattori immunologici
- Aldesleukin
- Vaccini
- Interleuchina-2
Altri numeri di identificazione dello studio
- 2006LS046
- UMN-0701M01001 (Altro identificatore: IRB, University of Minnesota)
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
prodotto fabbricato ed esportato dagli Stati Uniti
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