Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma

Melanoma Clinical Trial

Official title:

Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02403778
• Other study ID #: 14-0948.cc
• Status: Completed
• Phase: Phase 2
• Start date: December 17, 2015
• Est. completion date: January 18, 2023

Study information

• Verified date: September 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.

Description:

The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 18, 2023
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Patients over the age of 18 year.

• Patients diagnosed with advanced melanoma.

• Patients that are considered candidates for ipilimumab therapy.

• Patients able to understand and willing to sign a written informed consent documents.

• Patients willing to have regular blood draws, one before treatment and four during or after treatment.

Exclusion Criteria:

• Patients under the age of 18.

• Patients with Stage I or II, melanoma who are not candidates for Ipilimumab.

• Patients that have received systemic treatments within four weeks prior to the beginning of treatment.

• Women that are pregnant or nursing.

• Patients taking immunosuppressive medications.

• Patients with active autoimmune disease.

• Patients with known sensitivity to retinoic acid derivatives.

• Patients with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin > 2.5 × ULN.

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• VESANOID
All-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL).
• Ipilimumab
Ipilimumab is current standard of care treatment for melanoma.

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (1)

Tobin RP, Jordan KR, Robinson WA, Davis D, Borges VF, Gonzalez R, Lewis KD, McCarter MD. Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab. Int Immunopharmacol. 2018 Oct;63:282-291. doi: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events	Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.	Up to 2 years from the time of study enrollment for each patient.
Primary	MDSC Frequency	The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.	84 and 130 days following the first treatment
Primary	MDSC Suppressive Function	MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.	4 weeks prior to start, Midway thru and at least 30 days post final infusion
Secondary	Changes in the Frequency of Tumor-specific T Cell Responses	Changes in the frequency of tumor-specific T cell responses attributable to the addition of VESANOID to standard ipilimumab therapy will be determined by the frequency of Interferons (IFN)-gamma producing cells after stimulation with melanoma antigens.	4 weeks prior to start, Midway thru and at least 30 days post final infusion
Secondary	Unresectable Stage III and STAGE IV	Subjects will be followed for evidence of disease progression.	Up to 2 years from the time of study enrollment for each patient.