Stage IV MelanomaPhase 2NCT02054520
Immunotherapy Study for Patients With Stage IV Melanoma
A Phase 2 study testing HyperAcute®-Melanoma (HAM) Immunotherapy, Ipilimumab and Pembrolizumab in people with Stage IV Melanoma and Metastatic Melanoma, run by NewLink Genetics Corporation at 5 sites in United States.
Trial summary
The purpose of this study is to examine the effectiveness of immune checkpoint inhibitors (drugs called ipilimumab, nivolumab, or pembrolizumab), either given alone, or in combination with the experimental immunotherapy drug, dorgenmeltucel-L, for melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Melanoma, Metastatic Melanoma
- What is being tested?
- HyperAcute®-Melanoma (HAM) Immunotherapy, Ipilimumab and Pembrolizumab
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2014to 5 Jan 2021
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological/cytological diagnosis of melanoma. AJCC stage IV (any T, any N, M1), metastatic, progressive, refractory, melanoma.
- Patients may have advanced unresectable stage IV disease, resectable stave IV disease or recently resected stage IV disease (<10 weeks prior) with no apparent disease.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
- Serum albumin ≥3.0 gm/dL.
- Adequate organ function including:
- A. Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3, platelets ≥75,000/mm3, absolute lymphocyte count ≥475/mm3.
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- B. Hepatic: Serum total bilirubin ≤2.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤2.5 x ULN.
- C. Renal: Serum creatinine (sCr) ≤ 1.5 x upper limit of normal.
- Prior therapy for melanoma that may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or ≤2 different regiments of systemic chemotherapy, targeted therapy, or other experimental systemic therapies. Prior treatment with immune checkpoint inhibitors is not allowed.
- Patients must be ≥4 weeks since major surgery, radiotherapy, chemotherapy (6 weeks if they were treated with nitrosureas) or biotherapy/targeted therapies.
- Patients must have the ability to understand the study, its risks, side effects, potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA).
- Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last immunization.
Who cannot join
- Age <18-years-old.
- Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for
- ≥1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
- Other malignancy within five years, except the following may be eligible:
- patients curatively treated for localized squamous or basal cell carcinoma of the skin or for carcinoma in situ of the uterine cervix (CIN) or breast,
- patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated.
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- History of an allogeneic solid organ transplant or bone marrow transplant, or current active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
- Subjects taking systemic (parentally or orally) corticosteroid therapy for any reason, including replacement therapy for hypoadrenalism, are not eligible. Topical steroids are acceptable as are intranasal steroids.
- Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.
- Evidence of active autoimmune disease (e.g., systemic lupus erythematosis, rheumatoid arthritis, with the exception of vitiligo. Patients with a remote history of asthma or mild asthma are eligible.
- Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).
- Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc).
- Patients having previously undergone splenectomy.
- Patients with known hepatitis or unstable liver disease, and/or positive serologies for Hepatitis B or C and HIV.
- Patients with sickle-cell anemia or thalassemia major.
- Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Oncology Specialists
Niles, Illinois, 60714
University of Kansas Cancer Center
Westwood, Kansas
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase 2b Study of Immune Checkpoint Inhibition With or Without Dorgenmeltucel-L (HyperAcute Melanoma) Immunotherapy for Stage IV Melanoma Patients
The purpose of this study is to examine the effectiveness of immune checkpoint inhibitors (drugs called ipilimumab, nivolumab, or pembrolizumab), either given alone, or in combination with the experimental immunotherapy drug, dorgenmeltucel-L, for melanoma. We hypothesize that this form of combinatorial immunotherapy will result in tumor stabilization or shrinkage, significant prolongation of progression-free, disease-free or overall survival compared to the use of immune checkpoint inhibitors alone.
Read the detailed description
According to statistics of the American Cancer Society, an estimated 73,800 individuals will be diagnosed with melanoma and 9,900 will die of the disease in 2015 in the Unites States despite current therapy. This protocol attempts to exploit an approach to melanoma immunotherapy using a naturally occurring barrier to xenotransplantation in humans to increase the effectiveness of immunizing patients against their melanoma. The expression of the murine (1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of (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 2b study, patients with advanced stage melanoma will receive immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab per the treating physician's standard of care. In addition to the immune checkpoint therapy, half of the patients will also receive dorgenmeltucel-L. Dorgenmeltucel-L is 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 (1,3)GT gene. Endpoints of the study include safety assessments, efficacy, and immunological responses.
- Conditions
- Stage IV Melanoma, Metastatic Melanoma
- Being tested
- HyperAcute®-Melanoma (HAM) Immunotherapy, Ipilimumab, Pembrolizumab, Nivolumab
- Keywords
- Stage IV, metastatic melanoma
- 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 (HAM) ImmunotherapyDrug
Also called HyperAcute®-Melanoma, HAM, Dorgenmeltucel-L
IpilimumabDrug
Also called YERVOY, MDX-010, MDX-101
PembrolizumabDrug
Also called Keytruda
NivolumabDrug
Also called Opdivo
| Study group | Role | What they receive |
|---|---|---|
| Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab | Experimental | Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. Receives: Drug: HyperAcute®-Melanoma (HAM) Immunotherapy; Drug: Ipilimumab |
| Arm 2A Ipilimumab Alone | Active comparator | Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Receives: Drug: Ipilimumab |
| Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab | Experimental | Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. Receives: Drug: HyperAcute®-Melanoma (HAM) Immunotherapy; Drug: Nivolumab |
| Arm 2B Nivolumab alone | Active comparator | Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Receives: Drug: Nivolumab |
| Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab | Experimental | Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. Receives: Drug: HyperAcute®-Melanoma (HAM) Immunotherapy; Drug: Pembrolizumab |
| Arm 2C Pembrolizumab alone | Active comparator | Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters
To determine the safety of administration of immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab with or without dorgenmeltucel-L immunotherapy for patients with stage IV melanoma
Measured: 2 years
Clinical Response Rate
To estimate the clinical response rate of metastatic melanoma patients after immunotherapy with dorgenmeltucel-L immunotherapy plus immune checkpoint inhibition
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2014 (estimated)
- Study startJun 2014
- Primary completion5 Apr 2018
- Study completion5 Jan 2021
Why it stopped: Withdrawal of IND
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IV 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eugene Kennedy, MD, Study director, NewLink Genetics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02054520
- Sponsor's protocol ID
- NLG0304
- Other IDs
- 1303-1217
- Status last verified
- Mar 2023
- First submitted
- 3 Feb 2014
- Last updated
- 18 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Study of Immune Checkpoint Inhibition With or Without Dorgenmeltucel-L (HyperAcute Melanoma) Immunotherapy for Stage IV Melanoma Patients
- ClinicalTrials.gov ID
- NCT02054520
- Acronym / sponsor ID
- NLG0304
- Conditions
- Stage IV Melanoma, Metastatic Melanoma
- Keywords
- Stage IV, metastatic melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal of IND
- Enrolment
- 47 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- 5 Apr 2018 (actual)
- Study completion
- 5 Jan 2021 (actual)
- First posted
- 4 Feb 2014 (estimated)
- Results
- Posted 29 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the effectiveness of immune checkpoint inhibitors (drugs called ipilimumab, nivolumab, or pembrolizumab), either given alone, or in combination with the experimental immunotherapy drug, dorgenmeltucel-L, for melanoma. We hypothesize that this form of combinatorial immunotherapy will result in tumor stabilization or shrinkage, significant prolongation of progression-free, disease-free or overall survival compared to the use of immune checkpoint inhibitors alone.
Detailed description
According to statistics of the American Cancer Society, an estimated 73,800 individuals will be diagnosed with melanoma and 9,900 will die of the disease in 2015 in the Unites States despite current therapy. This protocol attempts to exploit an approach to melanoma immunotherapy using a naturally occurring barrier to xenotransplantation in humans to increase the effectiveness of immunizing patients against their melanoma. The expression of the murine (1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of (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 2b study, patients with advanced stage melanoma will receive immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab per the treating physician's standard of care. In addition to the immune checkpoint therapy, half of the patients will also receive dorgenmeltucel-L. Dorgenmeltucel-L is 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 (1,3)GT gene. Endpoints of the study include safety assessments, efficacy, and immunological responses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab | Experimental | Drug: HyperAcute®-Melanoma (HAM) Immunotherapy, Drug: IpilimumabArm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. |
| Arm 2A Ipilimumab Alone | Active comparator | Drug: IpilimumabArm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. |
| Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab | Experimental | Drug: HyperAcute®-Melanoma (HAM) Immunotherapy, Drug: NivolumabArm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. |
| Arm 2B Nivolumab alone | Active comparator | Drug: NivolumabArm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks |
| Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab | Experimental | Drug: HyperAcute®-Melanoma (HAM) Immunotherapy, Drug: PembrolizumabArm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. |
| Arm 2C Pembrolizumab alone | Active comparator | Drug: PembrolizumabArm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histological/cytological diagnosis of melanoma. AJCC stage IV (any T, any N, M1), metastatic, progressive, refractory, melanoma.
- Patients may have advanced unresectable stage IV disease, resectable stave IV disease or recently resected stage IV disease (<10 weeks prior) with no apparent disease.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
- Serum albumin ≥3.0 gm/dL.
- Adequate organ function including:
Key exclusion criteria (16 listed)
- Age <18-years-old.
- Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for
- ≥1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
- Other malignancy within five years, except the following may be eligible:
- History of an allogeneic solid organ transplant or bone marrow transplant, or current active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
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 (HAM) ImmunotherapyAlso: HyperAcute®-Melanoma, HAM, Dorgenmeltucel-L | Drug | Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab, Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab, Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab |
| IpilimumabAlso: YERVOY, MDX-010, MDX-101 | Drug | Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab, Arm 2A Ipilimumab Alone |
| PembrolizumabAlso: Keytruda | Drug | Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab, Arm 2C Pembrolizumab alone |
| NivolumabAlso: Opdivo | Drug | Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab, Arm 2B Nivolumab alone |
Primary outcome
Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters
Time frame: 2 years
To determine the safety of administration of immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab with or without dorgenmeltucel-L immunotherapy for patients with stage IV melanoma
Clinical Response Rate
Time frame: 2 years
To estimate the clinical response rate of metastatic melanoma patients after immunotherapy with dorgenmeltucel-L immunotherapy plus immune checkpoint inhibition
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Stage IV Melanoma
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BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
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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.
Eugene Kennedy, MD study director
NewLink Genetics Corporation
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HyperAcute®-Melanoma (HAM) Immunotherapy, Ipilimumab and Pembrolizumab in people with Stage IV Melanoma and Metastatic Melanoma, run by NewLink Genetics Corporation at 5 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?
The sponsor lists 12 inclusion and 16 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: stopped early, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 phase mean?
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 29 Apr 2020). 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 and Tolerability Assessed by Development of AEs and Laboratory Parameters (time frame: 2 years). The study lists 2 primary outcomes in all. 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 18 Apr 2023.