Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma

NCT ID: NCT00118274

Last Updated: 2021-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2010-02-28

Brief Summary

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with cyclophosphamide after surgery may cause a stronger immune response to kill any remaining tumor cells. It may also prevent or delay the recurrence of melanoma.

PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Detailed Description

OBJECTIVES:

Primary

• Determine the safety of adjuvant vaccine therapy comprising multi-epitope melanoma peptides (MP) and multi-epitope melanoma helper peptides (MHP) emulsified in Montanide ISA-51 in patients with resected stage IIB-IV melanoma.
• Determine the safety of administering cyclophosphamide before vaccination in these patients.
• Compare the magnitude of immune response against vaccination comprising MP in combination with either MHP or tetanus toxoid helper peptide (TET) emulsified in Montanide ISA-51 with vs without cyclophosphamide in these patients.

Secondary

• Compare the response rate and persistence of immune responses in patients treated with these regimens.
• Compare the magnitude of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
• Compare the response rate and persistence of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
• Determine the delayed-type hypersensitivity response to the peptide components of these vaccines in these patients.
• Compare, preliminarily, disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to HLA-type (HLA-A1 positive vs HLA-A2 positive, HLA-A1 negative, or -A3 negative vs HLA-A3 positive, or -A1 negative) and participating center (University of Virginia [UVA] vs non-UVA). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive vaccine comprising multi-epitope melanoma peptides (MP) and tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally (ID) and subcutaneously (SC) on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
• Arm II: Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine as in arm I.
• Arm III: Patients receive vaccine comprising MP and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 ID and SC on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
• Arm IV: Patients receive cyclophosphamide as in arm II. Patients then receive vaccine as in arm III.

Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 173 patients will be accrued for this study within 2 years.

Conditions

Melanoma (Skin)

Study Design

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

Study Groups

Arm I

Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.

Group Type: EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

multi-epitope melanoma peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

tetanus toxoid helper peptide

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

Arm II

Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.

Group Type: EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

multi-epitope melanoma peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

tetanus toxoid helper peptide

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

cyclophosphamide

Intervention Type: DRUG

Given IV

Arm III

Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.

Group Type: EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

melanoma helper peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

multi-epitope melanoma peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

Arm IV

Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.

Group Type: EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

melanoma helper peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

multi-epitope melanoma peptide vaccine

Intervention Type: BIOLOGICAL

Given intradermally and subcutaneously

cyclophosphamide

Intervention Type: DRUG

Given IV

Interventions

incomplete Freund's adjuvant

Given intradermally and subcutaneously

Intervention Type: BIOLOGICAL

melanoma helper peptide vaccine

Given intradermally and subcutaneously

Intervention Type: BIOLOGICAL

multi-epitope melanoma peptide vaccine

Given intradermally and subcutaneously

Intervention Type: BIOLOGICAL

tetanus toxoid helper peptide

Given intradermally and subcutaneously

Intervention Type: BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• No ocular melanoma
• Brain metastases allowed provided all of the following criteria are met:

• No more than 3 total brain metastases
• Each metastasis ≤ 2 cm in diameter at the time of study entry
• Each metastasis was completely removed by surgery or treated with stereotactic radiosurgery
• No evidence of brain metastasis progression since the most recent treatment

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 9 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 2.5 times ULN
• Lactic dehydrogenase ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Hepatitis C negative

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Immunologic

• HIV negative
• No known or suspected allergy to any component of the study vaccines
• No autoimmune disorder with visceral involvement
• No prior or active autoimmune disorder requiring cytotoxic or immunosuppressive therapy
• The following immunologic conditions are allowed:

• Laboratory evidence of autoimmune disease (e.g., positive anti-nuclear antibody titer) without symptoms
• Clinical evidence of vitiligo
• Other forms of depigmenting illness
• Mild arthritis requiring non-steroidal anti-inflammatory drugs

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Weight ≥ 110 lbs
• No uncontrolled diabetes

• Hemoglobin A1C < 7%
• No medical contraindication or potential problem that would preclude study compliance
• No other malignancy except squamous cell or basal cell skin cancer without known metastasis, carcinoma in situ of the breast (ductal or lobular) or cervix, or other successfully treated cancer without distant metastasis with no evidence of recurrence or metastasis for > 5 years
• No known active addiction to alcohol or drugs
• No recent (within the past year) or ongoing illicit IV drug use

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior vaccination with any of the synthetic peptides used in this study

• Prior vaccinations (containing agents other than the synthetic peptides used in this study) that resulted in recurrent disease during or after vaccine administration allowed provided the last vaccination was administered more than 12 weeks ago
• More than 4 weeks since prior and no concurrent interferon (e.g., Intron-A®), interleukins (e.g., Proleukin®), or growth factors (e.g., Procrit®, Aranesp®, or Neulasta®)
• More than 4 weeks since prior and no concurrent allergy desensitization injections
• No influenza vaccines for at least 2 weeks before or after study vaccine administration

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy, including nitrosoureas

Endocrine therapy

• More than 4 weeks since prior and no concurrent oral or parenteral corticosteroids
• No prior or concurrent inhaled steroids (e.g., Advair®, Flovent®, or Azmacort®)
• Prior or concurrent topical corticosteroids allowed

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since other prior and no concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 4 weeks since prior and no other concurrent investigational agents
• More than 30 days since prior and no concurrent participation in another clinical study

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Craig L Slingluff, Jr

OTHER

Sponsor Role: lead

Responsible Party

Craig L Slingluff, Jr

Professor of Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Craig L. Slingluff, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Countries

United States

References

Slingluff CL Jr, Petroni GR, Chianese-Bullock KA, Smolkin ME, Ross MI, Haas NB, von Mehren M, Grosh WW. Randomized multicenter trial of the effects of melanoma-associated helper peptides and cyclophosphamide on the immunogenicity of a multipeptide melanoma vaccine. J Clin Oncol. 2011 Jul 20;29(21):2924-32. doi: 10.1200/JCO.2010.33.8053. Epub 2011 Jun 20.

Reference Type: RESULT

PMID: 21690475 (View on PubMed)

Other Identifiers

UVACC-34104

Identifier Type: -

Identifier Source: secondary_id

UVACC-MEL-44

Identifier Type: -

Identifier Source: secondary_id

UVACC-GCRC-CLS013

Identifier Type: -

Identifier Source: secondary_id

UVACC-HITC-02620

Identifier Type: -

Identifier Source: secondary_id

MDA-2005-0070

Identifier Type: -

Identifier Source: secondary_id

11491

Identifier Type: -

Identifier Source: org_study_id