Immunotherapy Study for Patients With Stage IV Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by NewLink Genetics Corporation
Sponsor:
Information provided by (Responsible Party):
NewLink Genetics Corporation
ClinicalTrials.gov Identifier:
NCT02054520
First received: February 3, 2014
Last updated: October 28, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Stage IV Melanoma
Metastatic Melanoma
Drug: HyperAcute®-Melanoma (HAM) Immunotherapy
Drug: Ipilimumab
Drug: Pembrolizumab
Drug: Nivolumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2b Study of Immune Checkpoint Inhibition With or Without Dorgenmeltucel-L (HyperAcute Melanoma) Immunotherapy for Stage IV Melanoma Patients

Resource links provided by NLM:


Further study details as provided by NewLink Genetics Corporation:

Primary Outcome Measures:
  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    To estimate the clinical response rate of metastatic melanoma patients after immunotherapy with dorgenmeltucel-L immunotherapy plus immune checkpoint inhibition


Secondary Outcome Measures:
  • Clinical Activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To estimate the disease-free survival (DFS), progression-free survival (PFS), overall survival (OS) and duration of overall response, duration of complete response (CR) and duration of stable disease (SD) of patients with stage IV melanoma treated with immune checkpoint inhibition with or without dorgenmeltucel-L immunotherapy.

  • Anti-tumor Immune Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To measure anti-tumor immune responses in melanoma metastases in responding and non-responding patients.

  • Immune Activation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To further determine whether the humoral and cellular mediated arms of the host immune system are activated secondary to dorgenmeltucel-L immunotherapy combined with immune checkpoint inhibition.

  • Anti-Tumor Mechanism [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To perform correlative studies of patient samples (blood and tumor when available) to determine the mechanism of any observed anti-tumor effect.


Estimated Enrollment: 100
Study Start Date: June 2014
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HyperAcute®-Melanoma (HAM) Immunotherapy + Ipilimumab
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
Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L
Drug: Ipilimumab
Other Names:
  • YERVOY
  • MDX-010
  • MDX-101
Active Comparator: Ipilimumab Alone
Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses.
Drug: Ipilimumab
Other Names:
  • YERVOY
  • MDX-010
  • MDX-101
Active Comparator: Nivolumab Alone
Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks
Drug: Nivolumab
Other Name: Opdivo
Active Comparator: Pembrolizumab Alone
Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks
Drug: Pembrolizumab
Other Name: Keytruda
Experimental: HyperAcute®-Melanoma (HAM) Immunotherapy + nivolumab
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
Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L
Drug: Nivolumab
Other Name: Opdivo
Experimental: HyperAcute®-Melanoma (HAM) Immunotherapy + pembrolizumab
Arm 2C 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
Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L
Drug: Pembrolizumab
Other Name: Keytruda

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02054520

Locations
United States, Illinois
Oncology Specialists Recruiting
Niles, Illinois, United States, 60714
Contact: Anu Chakrabarty    847-410-0660    achakrabarty@oncmed.net   
Principal Investigator: Sigrun Hallmyer, M.D.         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Melanie Frees, RN, BSN, CCRC    319-356-1228    melanie-frees@uiowa.edu   
Principal Investigator: Mohammed Milhem, MD         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Stacey Lewis, RN    336-713-6927    stalewis@wakehealth.edu   
Principal Investigator: John H. Stewart, IV, MD         
United States, Tennessee
University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Shanna Overbey    865-305-5281    soverbey@utmck.edu   
Principal Investigator: Janakiraman Subramanian, MD         
Sponsors and Collaborators
NewLink Genetics Corporation
Investigators
Study Director: Eugene Kennedy, MD NewLink Genetics Corporation
  More Information

Additional Information:
Responsible Party: NewLink Genetics Corporation
ClinicalTrials.gov Identifier: NCT02054520     History of Changes
Other Study ID Numbers: NLG0304  1303-1217 
Study First Received: February 3, 2014
Last Updated: October 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by NewLink Genetics Corporation:
Stage IV
metastatic melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2016