Expired Study
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New York, New York 10021


Purpose:

Up to 24 patients with stage III or stage IV melanoma will be enrolled. Patients who are currently disease-free but at high risk for relapse are also eligible. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are eligible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies.


Study summary:

This study is designed to evaluate the safety and feasibility of intramuscular vaccination with gp75 DNA in patients with stage III or IV melanoma. Secondary objectives are to observe the patient for any evidence of anti-tumor response and to establish the optimal biologically effective dose. Up to 24 evaluable patients with stage III or IV metastatic melanoma or with stage III melanoma, currently disease-free, but at high risk for recurrence will be enrolled. Patients will be be enrolled into an assigned dose group and will receive five vaccinations of gp75. In order for dose escalation to proceed, only one patient in the current dose group may have demonstrated a dose limiting toxicity (DLT). If a second patient experiences such toxicity then both patients will move down to the previous dose level, and the previous dose level will be considered to be the MTD. If no DLTs are encountered, patients will continue on study at the assigned dose level. Any patient experiencing a DLT will not receive further vaccination until the toxicity has resolved. Patients exhibiting both serological and stable/clinical response after receiving the fifth vaccination will be eligible to receive booster vaccinations. An additional patient will be accrued to the dose level for every patient that progresses prior to the fifth vaccination.


Criteria:

Inclusion Criteria: 1. The patient has a diagnosis of American Joint Commission on Cancer (AJCC) stage 111 or IV malignant melanoma. A patient who is free of disease after surgical resection of stage 111 or IV disease, but at high risk (defined as a primary tumor >4 rnm, satellite or in-transit lesions, one or more positive lymph nodes or distant metastases) for recurrence is also eligible. A patient with metastatic disease may have no more than five sites of disease. The skin represents one site regardless of the number of lesions. Stage 111 melanoma is defined as a pT4 primary tumor (>4m in depth or Clark level 5) in-transit metastases, satellites lesions or regional lymph nodes involved with melanoma.Pathology slides must be reviewed by the investigational site's Department of Pathology. 2. The patient's Karnofsky performance status is 280 at study entry. 3. The patient has given signed informed consent. 4. The patient has had surgery for their melanoma at least 6 months prior to study entry, or has had prior interferon therapy, or developed unacceptable toxicities to interferon therapy, or has a pre-existing condition(s) that precludes the patient fkom receiving interferon treatment. 5. The patient is 21 8 years of age. 6. The patient must have completed any prior irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) at least 30 days prior to study entry. 7. The patient has adequate hematologic function as defined as a platelet count 2100,000/mm3 and white blood cell (WBC) level 23,000/mm3. 8. The patient has serum lactose dehydrogenase (LDH) within normal range and a serum creatinine level <2.0 mg/dL. 9. The patient agrees to use effective contraception if procreative potential exists. Exclusion Criteria: 1. The patient has stage I11 disease otherwise eligible to receive standard of care melanoma therapy. 2. The patient has a medical condition or use of medication (eg, corticosteroids) that might make it difficult for the patient to complete the full course of treatments or to respond immunologically to them, in the opinion of the investigator. 3. The patient has received irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) within 30 days prior to study entry. 4. The patient is pregnant (confirmed by serum beta human chorionic gonadotropin [PHCG], if applicable) or is breast feeding. 5. The patient has received any investigational agents within 30 days of study entry. 6. The patient has received prior cancer vaccine therapy. 7. The patient has evidence of central nervous system (CNS) metastasis. 8. The patient has evidence of an ocular abnormality, as detected by a slit-lamp ophthalmologic examination, within 4 weeks prior to study entry.


Study is Available At:


Original ID:

CP09-0001


NCT ID:

NCT00034554


Secondary ID:


Study Acronym:


Brief Title:

Study of gp75 Vaccine in Patients With Stage III and IV Melanoma


Official Title:

Phase I Study of gp75 DNA Vaccine in Patients With AJCC Stage III and IV Melanoma


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

ImClone LLC


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

5


Number of Groups:

0


Total Enrollment:

31


Enrollment Type:

Actual


Overall Contact Information

Official Name:E-mail: ClinicalTrials@ ImClone.com
Study Chair
ImClone LLC

Study Dates

Start Date:March 2002
Completion Date:September 2004
Completion Type:Actual
Primary Completion Date:September 2004
Primary Completion Type:Actual
Verification Date:December 2009
Last Changed Date:April 8, 2010
First Received Date:April 30, 2002

Study Outcomes

Outcome Type:Primary Outcome
Measure:Evaluate the safety and feasibility of intramuscular vaccination with gp75 DNA in patients with stage III or IV melanoma.
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Observe patients for any evidence of anti-tumor response, which is generated after vaccination.
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Establish the optimal biologically effective dose, defined as the lowest dose that correlates the production of anti-gp75 antibodies.
Safety Issues:False

Study Interventions

Intervention Type:Biological
Name:gp75 DNA vaccine
Description:6 patients will be enrolled in each of the 5 vaccination groups. Patients in vaccination groups 1-3 will receive a total of 5(1 mL) vaccinations. Patients assigned to vaccination group 4 will receive a total of 5 (2.0 mL) vaccinations administered as 2 1 mL injections. Patients assigned to vaccination group 5 will receive a total of 5 (4.0 mL or 8.0 mg)vaccinations administered as 4 1 mL injections per vaccination treatment Patients will receive gp75 DNA vaccinations every 3 weeks for 5 vaccinat
Arm Name:1

Study Arms

Study Arm Type:Experimental
Arm Name:1
Description:0.1mg
Study Arm Type:Experimental
Arm Name:2
Description:0.5mg
Study Arm Type:Experimental
Arm Name:3
Description:2.0mg
Study Arm Type:Experimental
Arm Name:4
Description:4.0mg
Study Arm Type:Experimental
Arm Name:5
Description:8.0mg

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:ImClone LLC
Agency Class:Other
Agency Type:Collaborator
Agency Name:Memorial Sloan-Kettering Cancer Center

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Bakker AB, Schreurs MW, de Boer AJ, Kawakami Y, Rosenberg SA, Adema GJ, Figdor CG. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med. 1994 Mar 1;179(3):1005-9.
PMID:8113668
Reference Type:Reference
Citation:Eton O, Legha SS, Balch CM. Cutaneous melanoma. N Engl J Med. 1992 Jan 30;326(5):345-6; discussion 346-7. No abstract available.
PMID:1728744
Reference Type:Reference
Citation:Bowne WB, Srinivasan R, Wolchok JD, Hawkins WG, Blachere NE, Dyall R, Lewis JJ, Houghton AN. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med. 1999 Dec 6;190(11):1717-22.
PMID:10587362
Reference Type:Reference
Citation:Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med. 1997 Nov 17;186(10):1623-31.
PMID:9362523
Reference Type:Reference
Citation:Hamilton WB, Helling F, Lloyd KO, Livingston PO. Ganglioside expression on human malignant melanoma assessed by quantitative immune thin-layer chromatography. Int J Cancer. 1993 Feb 20;53(4):566-73.
PMID:8436430
Reference Type:Reference
Citation:Hara I, Nguyen H, Takechi Y, Gansbacher B, Chapman PB, Houghton AN. Rejection of mouse melanoma elicited by local secretion of interleukin-2: implicating macrophages without T cells or natural killer cells in tumor rejection. Int J Cancer. 1995 Apr 10;61(2):253-60.
PMID:7705956
Reference Type:Reference
Citation:Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, Deck RR, DeWitt CM, Orme IM, Baldwin S, D'Souza C, Drowart A, Lozes E, Vandenbussche P, Van Vooren JP, Liu MA, Ulmer JB. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893-8.
PMID:8705859
Reference Type:Reference
Citation:Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.
PMID:8170938
Reference Type:Reference
Citation:Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996 Jan;14(1):7-17.
PMID:8558223
Reference Type:Reference
Citation:Schuchter L, Schultz DJ, Synnestvedt M, Trock BJ, Guerry D, Elder DE, Elenitsas R, Clark WH, Halpern AC. A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group. Ann Intern Med. 1996 Sep 1;125(5):369-75.
PMID:8702087
Reference Type:Reference
Citation:Sun WH, Burkholder JK, Sun J, Culp J, Turner J, Lu XG, Pugh TD, Ershler WB, Yang NS. In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2889-93.
PMID:7708743
Reference Type:Reference
Citation:Ugen KE, Nyland SB, Boyer JD, Vidal C, Lera L, Rasheid S, Chattergoon M, Bagarazzi ML, Ciccarelli R, Higgins T, Baine Y, Ginsberg R, Macgregor RR, Weiner DB. DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans. Vaccine. 1998 Nov;16(19):1818-21.
PMID:9795386
Reference Type:Reference
Citation:Vijayasaradhi S, Doskoch PM, Wolchok J, Houghton AN. Melanocyte differentiation marker gp75, the brown locus protein, can be regulated independently of tyrosinase and pigmentation. J Invest Dermatol. 1995 Jul;105(1):113-9.
PMID:7615964
Reference Type:Reference
Citation:Wang RF, Robbins PF, Kawakami Y, Kang XQ, Rosenberg SA. Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes. J Exp Med. 1995 Feb 1;181(2):799-804.
PMID:7836932
Reference Type:Reference
Citation:Wang RF, Appella E, Kawakami Y, Kang X, Rosenberg SA. Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes. J Exp Med. 1996 Dec 1;184(6):2207-16.
PMID:8976176
Reference Type:Reference
Citation:Wang R, Doolan DL, Le TP, Hedstrom RC, Coonan KM, Charoenvit Y, Jones TR, Hobart P, Margalith M, Ng J, Weiss WR, Sedegah M, de Taisne C, Norman JA, Hoffman SL. Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science. 1998 Oct 16;282(5388):476-80.
PMID:9774275
Reference Type:Reference
Citation:Weber LW, Bowne WB, Wolchok JD, Srinivasan R, Qin J, Moroi Y, Clynes R, Song P, Lewis JJ, Houghton AN. Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest. 1998 Sep 15;102(6):1258-64.
PMID:9739060
Reference Type:Reference
Citation:Wolchok JD, Livingston PO, Houghton AN. Vaccines and other adjuvant therapies for melanoma. Hematol Oncol Clin North Am. 1998 Aug;12(4):835-48, vii. Review.
PMID:9759582

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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