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Vaccination Plus Ontak in Patients With Metastatic Melanoma

Primary Purpose

Melanoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
4-peptide melanoma vaccine
Ontak
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring metastatic melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Melanoma with evidence of metastatic disease
  • Life expectancy of at least 12 weeks.
  • Karnofsky performance status index of greater than or equal to 80%.
  • Adequate hematopoietic, renal, and hepatic function, defined as:
  • Patient must express HLA-A2
  • Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells.
  • EKG without evidence of arrhythmia or changes that indicate acute ischemia.
  • Pulse oximetry showing oxygen saturation of at least 90% on room air.

Exclusion Criteria:

  • Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention.
  • Pregnant or nursing women.
  • Biological therapy in the 4 weeks prior to the start of dosing.
  • Patients with intrinsic immunosuppression, including seropositivity for HIV antibody.
  • Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C.
  • Concurrent systemic corticosteroids (except physiologic replacement doses)or other immunosuppressive drugs (eg. cyclosporin A).
  • Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent.
  • Active or history of autoimmune disease
  • Active gastrointestinal bleeding or uncontrolled peptic ulcer disease.
  • Presence of untreated brain metastases.

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Vaccine Alone

Vaccine plus Ontak

Arm Description

Subjects received vaccine immunization injected intra-dermally or subcutaneously on day 1. The vaccine was an emulsification consisting of 250 mcg each of the following peptides: Melan-A, gp100, MAGE-3, and NA17 as well as GM-CSF 125 mcg and Montanide. A second and third vaccination was given at 2 weeks and 4 weeks after the first. If there was no evidence of cancer progression, additional courses of three vaccinations administered at 2 week intervals were administered until disease progression.

Subjects in Vaccine plus Ontak received the same vaccination strategy as Vaccine alone group but additionally received a single dose of denileukin diftitox(18 mcg/kg) 4 days prior to the first vaccine administration

Outcomes

Primary Outcome Measures

Clinical Response Outcome
Proportion of Patients With a Best Response of Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). Response was evaluated every 6 weeks based on Response Evaluation In Solid Tumor (RECIST) version 1.1. Per RECIST v1.1 for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions

Secondary Outcome Measures

Full Information

First Posted
August 9, 2007
Last Updated
January 6, 2021
Sponsor
University of Chicago
Collaborators
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00515528
Brief Title
Vaccination Plus Ontak in Patients With Metastatic Melanoma
Official Title
Randomized Phase II Study of Multipeptide Vaccination With or Without Regulatory T Cell Depletion Using Ontak in Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
The immune monitoring data failed to demonstrate an improvement in any biologic endpoint with denileukin diftitox.
Study Start Date
April 23, 2007 (Actual)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
Eisai Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if an experimental melanoma vaccine can produce an immune response in patients with metastatic melanoma, and if combining this vaccine with the drug Ontak can improve these immune responses. It is also hoped that this will lead to tumor shrinkage.
Detailed Description
This is an open-label, randomized phase II, single institution study comparing administration of a 4-peptide melanoma vaccine alone or post-Ontak, in patients with metastatic melanoma. Treatment: Cohort A: Vaccine alone. Patients will receive immunization with an emulsion of 4 melanoma peptides (250 mcg each)/GM-CSF/Montanide injected intradermally/subcutaneously on day 1. A second vaccination will be given 2 weeks later and a third vaccination 2 weeks after that. Patients will be re-evaluated around week 6 and can continue courses of 3 vaccinations (one every 2 weeks) until disease progression. Cohort B: Ontak plus vaccine. Patients will receive Ontak (18 mcg/kg) intravenously on day -4 for one dose. On day 0, they will receive the first immunization with an emulsion of 4 melanoma peptides (250 mcg each)/GM-CSF/Montanide injected intradermally/subcutaneously. A second vaccination will be given 2 weeks later and a third vaccination 2 weeks after that. Patients will be re-evaluated around week 6 and can continue courses of 3 vaccinations (one every 2 weeks) until disease progression. However, no further Ontak will be given. Duration: Patients may remain on study until disease progression, unacceptable toxicity, patient choice to withdraw, or physician decision to discontinue therapy (due to intervening illness, poor patient compliance, or other situation that would increase patient risk).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
metastatic melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vaccine Alone
Arm Type
Experimental
Arm Description
Subjects received vaccine immunization injected intra-dermally or subcutaneously on day 1. The vaccine was an emulsification consisting of 250 mcg each of the following peptides: Melan-A, gp100, MAGE-3, and NA17 as well as GM-CSF 125 mcg and Montanide. A second and third vaccination was given at 2 weeks and 4 weeks after the first. If there was no evidence of cancer progression, additional courses of three vaccinations administered at 2 week intervals were administered until disease progression.
Arm Title
Vaccine plus Ontak
Arm Type
Experimental
Arm Description
Subjects in Vaccine plus Ontak received the same vaccination strategy as Vaccine alone group but additionally received a single dose of denileukin diftitox(18 mcg/kg) 4 days prior to the first vaccine administration
Intervention Type
Biological
Intervention Name(s)
4-peptide melanoma vaccine
Intervention Description
Experimental cancer vaccine given as a shot under the skin once every two weeks
Intervention Type
Drug
Intervention Name(s)
Ontak
Intervention Description
A single dose of Ontak given as an intravenous infusion over 30 minutes, 4 days before the first vaccine is given.
Primary Outcome Measure Information:
Title
Clinical Response Outcome
Description
Proportion of Patients With a Best Response of Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). Response was evaluated every 6 weeks based on Response Evaluation In Solid Tumor (RECIST) version 1.1. Per RECIST v1.1 for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Melanoma with evidence of metastatic disease Life expectancy of at least 12 weeks. Karnofsky performance status index of greater than or equal to 80%. Adequate hematopoietic, renal, and hepatic function, defined as: Patient must express HLA-A2 Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells. EKG without evidence of arrhythmia or changes that indicate acute ischemia. Pulse oximetry showing oxygen saturation of at least 90% on room air. Exclusion Criteria: Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention. Pregnant or nursing women. Biological therapy in the 4 weeks prior to the start of dosing. Patients with intrinsic immunosuppression, including seropositivity for HIV antibody. Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C. Concurrent systemic corticosteroids (except physiologic replacement doses)or other immunosuppressive drugs (eg. cyclosporin A). Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent. Active or history of autoimmune disease Active gastrointestinal bleeding or uncontrolled peptic ulcer disease. Presence of untreated brain metastases.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Gajeweski, MD, PhD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27330808
Citation
Luke JJ, Zha Y, Matijevich K, Gajewski TF. Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial. J Immunother Cancer. 2016 Jun 21;4:35. doi: 10.1186/s40425-016-0140-2. eCollection 2016.
Results Reference
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Vaccination Plus Ontak in Patients With Metastatic Melanoma

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