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Melanoma (Skin)Phase 1/2NCT00118274

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

A Phase 1/2 study testing incomplete Freund's adjuvant, melanoma helper peptide vaccine and multi-epitope melanoma peptide vaccine in people with Melanoma (Skin), run by Craig L Slingluff, Jr at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Melanoma (Skin)
What is being tested?
incomplete Freund's adjuvant, melanoma helper peptide vaccine and multi-epitope melanoma peptide vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
3 sitesUnited States
Study dates
Mar 2005to Feb 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Fox Chase Cancer Center - Philadelphia

    Philadelphia, Pennsylvania, 19111-2497

Other trials in United States

About this study

Official title: A Multicenter Trial to Evaluate the Effects of Administration of Cyclophosphamide and Melanoma-Derived Helper Peptides on the Immunogenicity of a Class I MHC-Restricted Peptide-Based Vaccine in Participants With Resected Melanoma

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.

Read the 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)
Being tested
incomplete Freund's adjuvant, melanoma helper peptide vaccine, multi-epitope melanoma peptide vaccine, tetanus toxoid helper peptide, cyclophosphamide
Keywords
stage II melanoma, stage III melanoma, stage IV melanoma
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • incomplete Freund's adjuvantBiological

    Given intradermally and subcutaneously

  • melanoma helper peptide vaccineBiological

    Given intradermally and subcutaneously

  • multi-epitope melanoma peptide vaccineBiological

    Given intradermally and subcutaneously

  • tetanus toxoid helper peptideBiological

    Given intradermally and subcutaneously

  • cyclophosphamideDrug

    Given IV

Study groups in NCT00118274
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide
Arm IIExperimentalPatients 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.
Receives: Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Drug: cyclophosphamide
Arm IIIExperimentalPatients 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.
Receives: Biological: incomplete Freund's adjuvant; Biological: melanoma helper peptide vaccine; Biological: multi-epitope melanoma peptide vaccine
Arm IVExperimentalPatients 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.
Receives: Biological: incomplete Freund's adjuvant; Biological: melanoma helper peptide vaccine; Biological: multi-epitope melanoma peptide vaccine; Drug: cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of the Peptide Vaccines

    Number of participants with dose-limiting toxicities

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

Secondary outcomes (1)
  1. Immunogenicity (CD8+ T Cell Response to 12 Melanoma Peptides, 12MP) as Measured by Elispot Assay, up to Day 50

    The primary end point was the maximum cumulative circulating CD8+ T cell response to 12 melanoma peptides (12MP) measured by ELISpot assay over the first six vaccines (to day 50).

    Measured: 50 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2005 (estimated)
  2. Study startMar 2005
  3. Primary completionFeb 2010
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
170 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00118274
Sponsor's protocol ID
11491
Other IDs
UVACC-34104, UVACC-MEL-44, UVACC-GCRC-CLS013, UVACC-HITC-02620, MDA-2005-0070
Status last verified
Mar 2021
First submitted
8 Jul 2005
Last updated
20 Apr 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 21690475
  • Ninmer EK, Zhu H, Chianese-Bullock KA, von Mehren M, Haas NB, Ross MI, Dengel LT, Slingluff CL Jr. Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial. Nat Commun. 2024 Mar 22;15(1):2570. doi: 10.1038/s41467-024-46877-6.

    PubMed 38519525

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing incomplete Freund's adjuvant, melanoma helper peptide vaccine and multi-epitope melanoma peptide vaccine in people with Melanoma (Skin), run by Craig L Slingluff, Jr at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of the Peptide Vaccines (time frame: 30 days after receiving the last dose of study drug, up to week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00118274, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.

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