Autologous TriMix-DC Therapeutic Vaccine in Combination With Ipilimumab in Patients With Previously Treated Unresectable Stage III or IV Melanoma

NCT01302496 | Completed Phase 2

• 2 other identifiers: UZB-VUB-10-0012010-023058-35
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The CTLA-4 blocking monoclonal antibody ipilimumab (MDX-010, BMS-734016), has demonstrated anti-tumor activity in a subgroup of patients with Stage III (unresectable) or Stage IV melanoma (measurable per modified WHO criteria), who have received prior treatment with any regimen (non-experimental or experimental), except a CD-137 agonist or a CTLA4 inhibitor or agonist and relapsed, failed to respond (CR or PR) or did not tolerate that regimen (Wolchok, Neyns et al. 2009; O'Day, Maio et al. 2010). Ipilimumab exerts its therapeutic effect presumably by activating T-lymphocytes that infiltrate the tumor mass to destroy the malignant cells by mechanisms of cytotoxic cellular interaction. Autologous TriMix-DC vaccine can induce a T-cell repertoire that recognizes in a HLA-restricted way the melanoma associated antigens MAGE-A3, MAGE-C2, tyrosinase and gp100. Administration of ipilimumab together with TriMix-DC vaccine therapy may be a more effective treatment for patients with advanced melanoma as compared to either modality alone.

Conditions

Malignant Melanoma Stage III; Malignant Melanoma Stage IV

Keywords

Previously Treated; Unresectable; Stage III or IV Melanoma

Outcome Measures

Primary Outcomes (1)

• disease control rate according to the immune-related response criteria

  Response evaluation by PET/CT every 12 weeks following initiation of study treatment

Study Arms (1)

TriMix-DC and Ipilimumab

EXPERIMENTAL

Biological: TriMix-DC and ipilimumab

Interventions

TriMix-DC and ipilimumab BIOLOGICAL

Patients will receive 5 administrations of autologous TriMix-DC, administrations 2, 3, 4 and 5 will be preceded by ipilimumab (a CTLA-4 blocking monoclonal antibody, at a dose of 10 mg/kg). Patients who are free from progression according to the irRC will be offered ipilimumab maintenance administrations of ipilimumab (10mg/kg q12wks).

TriMix-DC and Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent;
• Accessible for treatment and follow-up;
• Histologically confirmed malignant melanoma; primary melanoma of the skin, or unknown primary site (patients with primary mucosa or uveal melanoma are not eligible).
• Measurable melanoma, as per irRC criteria;
• AJCC Stage III (unresectable) or Stage IV melanoma;
• Patient must have demonstrated one of the following in response to treatment with at least one prior regimen (non-experimental or experimental) with the exception of a CD137 agonist or PD-1 or CTLA-4 inhibitor or agonist:
• relapse following an objective response of PR or CR; or
• failed to demonstrate an objective response of PR or CR based on an assessment period of at least 12 weeks from prior regimen start; or
• inability to tolerate treatment due to toxicity;
• Have a complete set of baseline (i.e., Screening) digital images of lesions and radiographic images, including, but not limited to: brain, bone, chest, abdomen and pelvis.
• Required values for initial laboratory tests:
• WBC \> 2500/mm³ ANC \> 1500/ mm³ Platelets \> 75 x 103/uL Hemoglobin \> 9 g/dL (may be transfused) Creatinine \< 2.0 x ULN AST/ALT \< 2.5 x ULN for patients without liver metastasis, \< 5 times for liver metastases Bilirubin \< 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
• ECOG performance status of 0 or 1;
• Life expectancy of \> 16 weeks;

You may not qualify if:

• Evidence of brain metastases on brain imaging (i.e., MRI or contrast CT);
• Primary ocular or mucosal melanoma;
• Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
• A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist, or PD-1 antagonist;.
• Concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses);
• Concomitant therapy with and need of uninterrupted therapeutic anticoagulation (e.g. because of a recent thrombo-embolic event or cardiac valve prothesis).
• Previous treatment with other investigational products, including cancer immunotherapy, within 30 days preceding study recruitment;
• Previous treatment in another ipilimumab clinical trial or prior treatment with a CD137 agonist, CTLA-4 inhibitor or agonist;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
• Women of childbearing potential (WOCBP), defined above in Section 4.1, who:
• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
• have a positive pregnancy test at baseline, or

Sponsors & Collaborators

• Bart Neyns: lead
• Vrije Universiteit Brussel: collaborator

Study Sites (1)

UZ Brussel

Jette, Brabant, 1090, Belgium

Location

Related Publications (1)

• De Keersmaecker B, Claerhout S, Carrasco J, Bar I, Corthals J, Wilgenhof S, Neyns B, Thielemans K. TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma. J Immunother Cancer. 2020 Feb;8(1):e000329. doi: 10.1136/jitc-2019-000329.

  PMID: 32114500 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: February 23, 2011
• First Posted: February 24, 2011
• Study Start: February 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2017
• Last Updated: March 29, 2021

Record last verified: 2021-03

Locations

BE (1)