Malignant MelanomaPhase 1/2NCT00300612
Vaccine Treatment for Advanced Malignant Melanoma
A Phase 1/2 study testing HyperAcute-Melanoma Vaccine in people with Malignant Melanoma, run by NewLink Genetics Corporation at 1 site in United States.
Trial summary
This 2-phase study will determine the safety of treating patients with malignant melanoma with the genetically engineered HyperAcute-Melanoma vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- HyperAcute-Melanoma Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Sep 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis of malignant melanoma. (pathology must be reviewed by Pathology Department)
- AJCC Stage IIIC (any T, N1b, N2b, N3, M0) or Stage IV (any T, any N, M1), metastatic, progressive, refractory, recurrent, or high risk of recurrence malignant melanoma.
- Adult patients > or = to 18 years of age
- Measurable or non-measurable disease.
- Patient is > or = to 4 weeks past major surgery, radiotherapy, chemotherapy. (6 weeks if treated with a nitrosureas) or biotherapy/targeted therapies and has recovered from the toxicity of prior treatment to < or = to Grade 1, exclusive of alopecia or fatigue.
- Hemoglobin > or = to 10.0 gm/dL, absolute granulocyte count > or = to 1500/ mm3,platelets > or = to 100,000/ mm3, absolute lymphocyte count > or = to 475/ mm3.
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- Total Bilirubin < or = to 1.5 ULN (mg/dL), ALT (SGPT) and AST (SGOT) < or = to 2.5 x ULN.
- Serum creatinine < or = to 1.5 x ULN, or creatinine clearance > or = to 50 mL/min.
- Serum albumin > or = to 3.0 gm/dL.
- ECOG performance status < or = to 2.
- All On-Study Test results are < or = to Grade I toxicity for patient to be eligible for study, except for serum LDH. PT, PTT must be < or = to 1.5 x ULN except for patients who are on therapeutic anticoagulant therapy.
- Negative serologies for Hepatitis B, Hepatitis C, and HIV
- Ability to give informed consent and express a willingness to meet all the expected requirements of the protocol including using contraception as outlined in the consent form.
- Expected survival > 6 months. NOTE: Prior therapy for melanoma may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or < or = to 2 different chemotherapy regimens and other experimental therapies.
Who cannot join
- Subject has an active CNS metastases or carcinomatous meningitis. Subjects with CNS lesions that have been treated and show no evidence of progression on CT/MRI for > or = to 3 months are eligible.
- Hypercalcemia > 2.9 mmol/L, unresponsive to standard therapy (IV hydration, diuretics calcitonin and/or bisphosphate therapy)
- Subject is any of the following: HIV positive, history or hepatitis C virus infection, acute or chronic active hepatitis B virus infection (HbsAg positive).
- Subject has had splenectomy.
- Subject has had other malignancy within five years, and probability of recurrence of prior malignancy is >5%. (if less than 5% subject is eligible) SEE NOTE1
- Subject has history of organ transplant or currently taking active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
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- Subject is currently receiving systemic corticosteroid therapy for any reason. SEE NOTE2
- Subject has significant or uncontrolled congestive heart failure, myocardial infarction or significant ventricular arrhythmias within the last six months or significant pulmonary dysfunction.
- Subject has an active infection or antibiotics within 1-week prior to study,including unexplained fever (temp > 38.1C)
- Subject has an autoimmune disease (systemic lupus erythematosis, active rheumatoid arthritis, etc.) with the exception of vitiligo. SEE NOTE3.
- Subject has a serious medical condition that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis)
- Subject has any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with an aspect of the study.
- Subject has a known allergy to a component of the alpha(1,3)galactosyltransferase tumor vaccine or cell lines from which it is derived.
- Subject is pregnant or nursing.
- NOTE1: Subjects curatively treated for squamous and basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or subjects with a history of malignant tumor in the past that has been disease free for at least five years are also eligible for this study.
- NOTE2: Subject's receiving inhaled or topical corticosteroids are eligible. Subjects who require systemic corticosteroid therapy after beginning vaccination will be removed from the study.
- NOTE3: Subjects with a remote history of asthma or mild active asthma are eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase I/II Study of Dorgenmeltucel-L (HyperAcute Melanoma) an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Refractory or Recurrent Malignant Melanoma
This 2-phase study will determine the safety of treating patients with malignant melanoma with the genetically engineered HyperAcute-Melanoma vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed melanoma cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 18 years of age or older with malignant melanoma may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Read more
Participants will receive twelve vaccinations two weeks apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Monthly blood samples will be drawn during the 6 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 3 months for the remaining first year (6 months) after vaccination and then every 6 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
Medical history and physical examination Blood tests X-rays and various scans (nuclear medicine/CT/MRI) FACT-G Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, monthly during treatment, and during follow-up visits after completing the treatment. It includes questions on the severity of cancer symptoms and the ability to perform normal activities of daily life.
Read the detailed description
According to statistics of the American Cancer Society, an estimated 55,000 individuals will be diagnosed with malignant melanoma and 8,000 will die of the disease this year in the Unites States despite all current therapy. This protocol attempts to exploit an approach to melanoma vaccine therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their melanoma The expression of the murine alpha(1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of alpha(1,3)galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with advanced stage melanoma will undergo a series of twelve intradermal injections with a trivalent vaccine composed of irradiated allogeneic melanoma cell lines (HAM-1, HAM-2 and HAM-3). These cell lines have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha(1,3)GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
- Conditions
- Malignant Melanoma
- Being tested
- HyperAcute-Melanoma Vaccine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HyperAcute-Melanoma VaccineBiological
Also called HAM-1, HAM-2, and HAM-3
Cells will be injected intradermally every two weeks for twelve vaccinations. If the patient completes all twelve vaccinations, dosage will vary from a total of 1.3 x 109 to 3.8 x 109 HyperAcute™-Melanoma Vaccine cells administered.
| Study group | Role | What they receive |
|---|---|---|
| vaccine group | Experimental | Not described Receives: Biological: HyperAcute-Melanoma Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the side effects, dose-limiting toxicity and maximum tolerated dose.
Measured: 6 months
Secondary outcomes (1)
To assess tumor response and immunological response.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2006 (estimated)
- Study startMar 2006
- Primary completionSep 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Ronald C. DeConti, M.D., Principal investigator, University of South FloridaCharles J. Link, M.D., Study chair, NewLink Genetics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00300612
- Sponsor's protocol ID
- NLG0104
- Other IDs
- OBA#0404-640
- Status last verified
- May 2020
- First submitted
- 7 Mar 2006
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Dorgenmeltucel-L (HyperAcute Melanoma) an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Refractory or Recurrent Malignant Melanoma
- ClinicalTrials.gov ID
- NCT00300612
- Acronym / sponsor ID
- NLG0104
- Conditions
- Malignant Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 9 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2-phase study will determine the safety of treating patients with malignant melanoma with the genetically engineered HyperAcute-Melanoma vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed melanoma cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 18 years of age or older with malignant melanoma may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Participants will receive twelve vaccinations two weeks apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Monthly blood samples will be drawn during the 6 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 3 months for the remaining first year (6 months) after vaccination and then every 6 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
Medical history and physical examination Blood tests X-rays and various scans (nuclear medicine/CT/MRI) FACT-G Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, monthly during treatment, and during follow-up visits after completing the treatment. It includes questions on the severity of cancer symptoms and the ability to perform normal activities of daily life.
Detailed description
According to statistics of the American Cancer Society, an estimated 55,000 individuals will be diagnosed with malignant melanoma and 8,000 will die of the disease this year in the Unites States despite all current therapy. This protocol attempts to exploit an approach to melanoma vaccine therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their melanoma The expression of the murine alpha(1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of alpha(1,3)galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with advanced stage melanoma will undergo a series of twelve intradermal injections with a trivalent vaccine composed of irradiated allogeneic melanoma cell lines (HAM-1, HAM-2 and HAM-3). These cell lines have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha(1,3)GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vaccine group | Experimental | Biological: HyperAcute-Melanoma Vaccine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological diagnosis of malignant melanoma. (pathology must be reviewed by Pathology Department)
- AJCC Stage IIIC (any T, N1b, N2b, N3, M0) or Stage IV (any T, any N, M1), metastatic, progressive, refractory, recurrent, or high risk of recurrence malignant melanoma.
- Adult patients > or = to 18 years of age
- Measurable or non-measurable disease.
- Patient is > or = to 4 weeks past major surgery, radiotherapy, chemotherapy. (6 weeks if treated with a nitrosureas) or biotherapy/targeted therapies and has recovered from the toxicity of prior treatment to < or = to Grade 1, exclusive of alopecia or fatigue.
Key exclusion criteria (17 listed)
- Subject has an active CNS metastases or carcinomatous meningitis. Subjects with CNS lesions that have been treated and show no evidence of progression on CT/MRI for > or = to 3 months are eligible.
- Hypercalcemia > 2.9 mmol/L, unresponsive to standard therapy (IV hydration, diuretics calcitonin and/or bisphosphate therapy)
- Subject is any of the following: HIV positive, history or hepatitis C virus infection, acute or chronic active hepatitis B virus infection (HbsAg positive).
- Subject has had splenectomy.
- Subject has had other malignancy within five years, and probability of recurrence of prior malignancy is >5%. (if less than 5% subject is eligible) SEE NOTE1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HyperAcute-Melanoma VaccineAlso: HAM-1, HAM-2, and HAM-3Cells will be injected intradermally every two weeks for twelve vaccinations. If the patient completes all twelve vaccinations, dosage will vary from a total of 1.3 x 109 to 3.8 x 109 HyperAcute™-Melanoma Vaccine cells administered. | Biological | vaccine group |
Primary outcome
To assess the side effects, dose-limiting toxicity and maximum tolerated dose.
Time frame: 6 months
1 secondary outcome
To assess tumor response and immunological response.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald C. DeConti, M.D. principal investigator
University of South Florida
Charles J. Link, M.D. study chair
NewLink Genetics Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HyperAcute-Melanoma Vaccine in people with Malignant Melanoma, run by NewLink Genetics Corporation at 1 site 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?
The sponsor lists 14 inclusion and 17 exclusion criteria. 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 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the side effects, dose-limiting toxicity and maximum tolerated dose. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2020.