Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

NCT ID: NCT00056134

Last Updated: 2018-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-10-31
• Study Completion Date: 2012-05-31

Brief Summary

RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma.

Detailed Description

OBJECTIVES:

• Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or HLA-A2.1-positive stage III or IV melanoma.
• Determine the safety and tolerability of these vaccinations in these patients.
• Determine tumor response in patients treated with these vaccinations.

OUTLINE:

• Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC are processed for the generation of dendritic cells (DC) to be used for vaccinations. DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.

Patients who show a tumor response (at least stable disease) may receive vaccination #5 and further booster vaccinations.

• Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6 additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692 in the absence of disease progession or unacceptable toxicity.

Patients are followed for 10 years.

PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Dendritic cell vaccine plus denileukin difitox

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed locoregional or metastatic cutaneous malignant melanoma

• Stage III or IV disease

• Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
• Stage IV: any pT, N1-2, M1a-b
• Surgically incurable
• Incurable with standard treatment (i.e., localized chemotherapy/limb perfusion for stage III, systemic chemotherapy for stage IV)
• Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III lesions may be measurable lymph nodes after incomplete resection and/or inoperable in transit metastases
• HLA-A1 and/or HLA-A2 expression by serologic HLA typing

• HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells
• No active CNS metastases

• Previously treated CNS metastases (e.g., excision of a single metastasis) allowed if no active disease present by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

• WBC greater than 2,500/mm^3
• Neutrophil count greater than 1,000/mm^3
• Lymphocyte count greater than 700/mm^3
• Platelet count greater than 75,000/mm^3
• Hemoglobin greater than 9 g/dL
• No bleeding disorders

Hepatic

• Bilirubin less than 2.0 mg/dL
• No hepatitis B or C

Renal

• Creatinine less than 2.5 mg/dL

Cardiovascular

• No clinically significant heart disease

Pulmonary

• No clinically significant respiratory disease

Immunologic

• No active systemic infection
• No immunodeficiency disease

• No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1
• No active autoimmune disease including, but not limited to:

• Lupus erythematosus
• Autoimmune thyroiditis or uveitis
• Multiple sclerosis
• Inflammatory bowel disease NOTE: Vitiligo allowed

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• No organic brain syndrome or significant psychiatric abnormality that would preclude study participation and follow-up
• No contraindication to leukapheresis
• No other active malignant neoplasms

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior systemic immunotherapy
• No concurrent immunotherapy during and for 2 weeks after last vaccination

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
• No concurrent chemotherapy during and for 2 weeks after last vaccination

Endocrine therapy

• No concurrent corticosteroids during and for 2 weeks after last vaccination

Radiotherapy

• No prior radiotherapy to the spleen
• Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or local complications such as compression)

Surgery

• See Disease Characteristics
• Recovered from prior surgery
• No prior splenectomy
• No prior organ allografts
• Concurrent surgery of selected metastases (e.g., pain or local complications such as compression) allowed

Other

• No other concurrent investigational drugs during and for 2 weeks after last vaccination
• No concurrent paramedical substance during and for 2 weeks after last vaccination
• No concurrent participation or intent to participate in another clinical trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Erlangen

OTHER

Sponsor Role: lead

Responsible Party

PD Dr. med. univ. Beatrice Schuler-Thurner

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerold Schuler

Role: STUDY_CHAIR

Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Locations

Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen

Erlangen, , Germany

Countries

Germany

References

Baur AS, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kampgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G. Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood. 2013 Sep 26;122(13):2185-94. doi: 10.1182/blood-2012-09-456988. Epub 2013 Aug 19.

Reference Type: DERIVED

PMID: 23958949 (View on PubMed)

Study Documents

Document Type: Publication

Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Baur AS1, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kämpgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G.

View Document

Document Type: Clinical Study Report

Denileukin diftitox (ONTAK) induces... Baur AS et al

View Document

Other Identifiers

ERLANGEN-ONTAK

Identifier Type: -

Identifier Source: secondary_id

EU-20246

Identifier Type: -

Identifier Source: secondary_id

CDR0000270762

Identifier Type: -

Identifier Source: org_study_id