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

NCT00118274 | Completed Phase 1 Results FDA Drug

• 6 other identifiers: 11491UVACC-34104UVACC-MEL-44UVACC-GCRC-CLS013UVACC-HITC-02620MDA-2005-0070
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 3

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.

Conditions

Melanoma (Skin)

Keywords

stage II melanoma; stage III melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• Safety of the Peptide Vaccines

  Number of participants with dose-limiting toxicities

  30 days after receiving the last dose of study drug, up to week 52

Secondary Outcomes (1)

• Immunogenicity (CD8+ T Cell Response to 12 Melanoma Peptides, 12MP) as Measured by Elispot Assay, up to Day 50

  50 days

Study Arms (4)

Arm I

EXPERIMENTAL

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.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide

Arm II

EXPERIMENTAL

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.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Drug: cyclophosphamide

Arm III

EXPERIMENTAL

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.

Biological: incomplete Freund's adjuvant; Biological: melanoma helper peptide vaccine; Biological: multi-epitope melanoma peptide vaccine

Arm IV

EXPERIMENTAL

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.

Biological: incomplete Freund's adjuvant; Biological: melanoma helper peptide vaccine; Biological: multi-epitope melanoma peptide vaccine; Drug: cyclophosphamide

Interventions

incomplete Freund's adjuvant BIOLOGICAL

Given intradermally and subcutaneously

Arm I; Arm II; Arm III; Arm IV

melanoma helper peptide vaccine BIOLOGICAL

Given intradermally and subcutaneously

Arm III; Arm IV

multi-epitope melanoma peptide vaccine BIOLOGICAL

Given intradermally and subcutaneously

Arm I; Arm II; Arm III; Arm IV

tetanus toxoid helper peptide BIOLOGICAL

Given intradermally and subcutaneously

Arm I; Arm II

cyclophosphamide DRUG

Given IV

Arm II; Arm IV

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed melanoma * Cutaneous, mucosal, or primary melanoma * Stage IIB-IV disease * Has undergone surgical resection or stereotactic radiosurgery for malignant melanoma ≥ 1 week but ≤ 6 months ago * No clinical or radiological evidence of disease after surgical resection or stereotactic radiosurgery by chest x-ray or CT scan\*, abdominal and pelvic CT scan\*, and head CT scan or MRI NOTE: \*Positron emission tomography scan/CT fusion scan may replace scans of the chest, abdomen, and pelvis * Must have ≥ 2 intact (undissected) axillary and/or inguinal lymph node basins * HLA-A1, -A2, or -A3 positive AND HLA-DR1, -DR4, -DR11, -DR13, or -DR15 positive * Ineligible for OR refused interferon * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 21690475 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

incomplete Freund's adjuvant; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Craig Slingluff
• Organization: University of Virginia

cls8h@virginia.edu

4349249311

Study Officials

• Craig L. Slingluff, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 11, 2005
• Study Start: March 1, 2005
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: April 20, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-03

Locations

US (3)