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Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma

3. Dezember 2017 aktualisiert von: Masonic Cancer Center, University of Minnesota

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.

Studienübersicht

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

21

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

    • Minnesota
      • Minneapolis, Minnesota, Vereinigte Staaten, 55455
        • Masonic Cancer Center, University of Minnesota

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Crossover-Aufgabe
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Andere Namen:
  • Proleukin
  • IL-2
  • Interleukin-2
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.
Andere Namen:
  • LMI vaccine
Aktiver Komparator: 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.
Andere Namen:
  • Proleukin
  • IL-2
  • Interleukin-2
Experimental: 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.
Andere Namen:
  • Proleukin
  • IL-2
  • Interleukin-2
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.
Andere Namen:
  • LMI vaccine

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Median Time of Progression-free Survival
Zeitfenster: 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.

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Clinical Response of Lesion(s)
Zeitfenster: 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
Overall Survival at 2 Years
Zeitfenster: 2 Years
Two year survival (alive at 2 years from randomization) rate of each treatment group.
2 Years
Overall Survival at 1 Year
Zeitfenster: 1 Year
One year survival (alive at 1 year from randomization) rate of each treatment group.
1 Year
Immune Response
Zeitfenster: 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.
48 hours After Study Medication

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Juni 2008

Primärer Abschluss (Tatsächlich)

1. Juni 2011

Studienabschluss (Tatsächlich)

1. Juni 2011

Studienanmeldedaten

Zuerst eingereicht

31. Juli 2008

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

31. Juli 2008

Zuerst gepostet (Schätzen)

1. August 2008

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

28. Dezember 2017

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

3. Dezember 2017

Zuletzt verifiziert

1. Dezember 2017

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Nein

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