Vaccination Plus Ontak in Patients With Metastatic Melanoma

NCT ID: NCT00515528

Last Updated: 2021-01-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-23
• Study Completion Date: 2016-03-31

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:

1. 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.

2. 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).

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaccine Alone

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.

Group Type: EXPERIMENTAL

4-peptide melanoma vaccine

Intervention Type: BIOLOGICAL

Experimental cancer vaccine given as a shot under the skin once every two weeks

Vaccine plus Ontak

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

Group Type: EXPERIMENTAL

4-peptide melanoma vaccine

Intervention Type: BIOLOGICAL

Experimental cancer vaccine given as a shot under the skin once every two weeks

Ontak

Intervention Type: DRUG

A single dose of Ontak given as an intravenous infusion over 30 minutes, 4 days before the first vaccine is given.

Interventions

4-peptide melanoma vaccine

Experimental cancer vaccine given as a shot under the skin once every two weeks

Intervention Type: BIOLOGICAL

Ontak

A single dose of Ontak given as an intravenous infusion over 30 minutes, 4 days before the first vaccine is given.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Gajeweski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27330808 (View on PubMed)

Other Identifiers

15232B

Identifier Type: -

Identifier Source: org_study_id