Vaccination Plus Ontak in Patients With Metastatic Melanoma

• Sponsor: University of Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00515528
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 17
• Location: 1
• Arms: 2
• Actual Duration (Months): 106.3
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: 4-peptide melanoma vaccine; Drug: Ontak	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Multipeptide Vaccination With or Without Regulatory T Cell Depletion Using Ontak in Patients With Metastatic Melanoma
• Actual Study Start Date: Apr 23, 2007
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: 4-peptide melanoma vaccine; Experimental cancer vaccine given as a shot under the skin once every two weeks
Experimental: 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	Biological: 4-peptide melanoma vaccine; Experimental cancer vaccine given as a shot under the skin once every two weeks; Drug: Ontak; A single dose of Ontak given as an intravenous infusion over 30 minutes, 4 days before the first vaccine is given.

Outcome Measures

Primary Outcome Measures

1. Clinical Response Outcome [6 weeks]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• Eisai Inc.

Investigators

• Principal Investigator: Thomas Gajeweski, MD, PhD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00515528
• Other Study ID Numbers: 15232B
• First Posted: Aug 13, 2007
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by University of Chicago: metastatic melanoma
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Arm/Group Title	Vaccine Alone	Vaccine Plus Ontak
Arm/Group 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.
Period Title: Overall Study
STARTED	10	7
COMPLETED	10	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vaccine Alone	Vaccine Plus Ontak	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	10	7	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	63	63
Sex: Female, Male (Count of Participants)
Female	2 20%	1 14.3%	3 17.6%
Male	8 80%	6 85.7%	14 82.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vaccine Alone	Vaccine Plus Ontak
Arm/Group 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.
Measure Participants	10	7
PR	1 10%	0 0%
SD	4 40%	4 57.1%
PD	5 50%	3 42.9%

Adverse Events

Time Frame	3 months
Arm/Group Title	Vaccine Alone		Vaccine Plus Ontak
Arm/Group 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.
All Cause Mortality
	Vaccine Alone		Vaccine Plus Ontak
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		1/7 (14.3%)
Serious Adverse Events
	Vaccine Alone		Vaccine Plus Ontak
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		2/7 (28.6%)
Congenital, familial and genetic disorders
Pericardial tamponade	0/10 (0%)		1/7 (14.3%)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)		1/7 (14.3%)
General disorders
Chest pain	1/10 (10%)		0/7 (0%)
Nervous system disorders
Syncope	1/10 (10%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Vaccine Alone		Vaccine Plus Ontak
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		7/7 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/10 (10%)		1/7 (14.3%)
Anemia	1/10 (10%)		1/7 (14.3%)
Gastrointestinal disorders
Nausea	2/10 (20%)		3/7 (42.9%)
Diarrhea	1/10 (10%)		0/7 (0%)
Constipation	1/10 (10%)		1/7 (14.3%)
Vomiting	0/10 (0%)		2/7 (28.6%)
General disorders
Injection Site Pain	7/10 (70%)		3/7 (42.9%)
Headache	9/10 (90%)		2/7 (28.6%)
Fatigue	1/10 (10%)		1/7 (14.3%)
Fever	1/10 (10%)		1/7 (14.3%)
Chills	2/10 (20%)		1/7 (14.3%)
Insomnia	1/10 (10%)		0/7 (0%)
Visual Problems	0/10 (0%)		1/7 (14.3%)
Neck Tightness	1/10 (10%)		0/7 (0%)
Weight Gain	0/10 (0%)		1/7 (14.3%)
Infections and infestations
Infection	0/10 (0%)		1/7 (14.3%)
Investigations
SGOT	1/10 (10%)		2/7 (28.6%)
SGPT	3/10 (30%)		3/7 (42.9%)
Absolute Neutrophil Count Decrease	0/10 (0%)		1/7 (14.3%)
Platelet Count Decreased	1/10 (10%)		0/7 (0%)
Creatinine Increased	2/10 (20%)		1/7 (14.3%)
Bilirubin increased	2/10 (20%)		0/7 (0%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)		2/7 (28.6%)
Hyperkalemia	0/10 (0%)		1/7 (14.3%)
Nervous system disorders
Neurological	3/10 (30%)		0/7 (0%)
Edema	0/10 (0%)		1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory	4/10 (40%)		4/7 (57.1%)
Rhinitis	1/10 (10%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)		2/7 (28.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.