Immunotherapy Study for Patients With Stage IV Melanoma

NCT02054520 | Terminated Phase 2 Results

• 2 other identifiers: NLG03041303-1217
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Stage IV Melanoma; Metastatic Melanoma

Keywords

Stage IV; metastatic melanoma

Outcome Measures

Primary Outcomes (2)

• 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

  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

  2 years

Study Arms (6)

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.

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.

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.

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

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.

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

Drug: Pembrolizumab

Interventions

HyperAcute®-Melanoma (HAM) Immunotherapy DRUG

Also known as: HyperAcute®-Melanoma, HAM, Dorgenmeltucel-L

Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab; Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab; Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab

Ipilimumab DRUG

Also known as: YERVOY, MDX-010, MDX-101

Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab; Arm 2A Ipilimumab Alone

Pembrolizumab DRUG

Also known as: Keytruda

Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab; Arm 2C Pembrolizumab alone

Nivolumab DRUG

Also known as: Opdivo

Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab; Arm 2B Nivolumab alone

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (5)

Oncology Specialists

Niles, Illinois, 60714, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

ATF7IP protein, human; Immunotherapy; Ipilimumab; pembrolizumab; Nivolumab

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)

Immunomodulation; Biological Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed. The enrollment and treatment phase of this trial was terminated early and the IND has been closed.

Results Point of Contact

• Title: Manager, Clinical Operations
• Organization: NewLink Genetics Corporation

csmith@linkp.com

515-598-5020

Study Officials

• Eugene Kennedy, MD

  NewLink Genetics Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 4, 2014
• Study Start: June 1, 2014
• Primary Completion: April 5, 2018
• Study Completion: January 5, 2021
• Last Updated: April 18, 2023
• Results First Posted: April 29, 2020

Record last verified: 2023-03

Locations

US (5)