Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-MT) for Patients With Melanoma.

A Phase 1/2, Open Label, Non-Randomized Dose Escalation Study to Evaluate the Safety, Tolerability, Immune Response and Clinical Response of Multiple Doses of MKC1106-MT in Subjects With Advanced Melanoma

A dose comparison of a multi-component active immunotherapy designed to stimulate an immune reaction to specific tumor associated antigens which are highly expressed on melanomas.

Study Overview

• Status: Completed
• Conditions: Advanced Melanoma; Stage III and IV Melanoma
• Intervention / Treatment: Biological: Biological: MKCC1106-MT; Biological: Biological: MKC1106-MT

Detailed Description

The multi-component active immunotherapy, MKC1106-MT, consists of 1 plasmid dose and 2 peptides doses designed to stimulate an immune reaction to two tumor associated antigens (Melan-A and tyrosinase). The plasmid component will be administered on Days 1,4, 15 and 18 of each treatment cycle followed by administration of peptides on Days 29 and 32 of the treatment cycle. All components will be administered separately into superficial inguinal lymph nodes under ultrasound guidance.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90034
      • UCLA Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center University of So Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Confirmed diagnosis of locally advanced or metastatic melanoma (American Joint Committee on Cancer [AJCC 6th edition] stage IIIB, IIIC or IV) that is refractory to standard therapy or for which no curative standard therapy exists.

Patients enrolled in the Phase 2 portion of the trial must have measurable disease by the RECIST criteria ECOG performance status of 0 or 1 Life expectancy = 3 months 18 years of age or older at screening evaluation Positive for HLA-A2, and more precisely, express A*0201 as assessed by DNA typing Tumor material from prior biopsy / surgical resection available for analysis of expression of melanoma specific antigens Adequate bone marrow reserve as evidenced by: Absolute neutrophil count (ANC) = 1,000/?L & Platelet count = 75,000/?L Adequate renal function as evidenced by: serum creatinine = 1.5 mg/dL Adequate hepatic function as evidenced by: Serum total bilirubin = 2.0 mg/dL & SGOT/SGPT = 3 times the ULN for the reference lab (= 5 the ULN for the reference lab for subjects with known hepatic metastases) Subjects must have recovered to at least baseline or Grade 1 toxicity from the effects of any prior surgery, radiotherapy or other therapies including but not limited to chemotherapy Women of childbearing potential as well as fertile men and their partners must agree to use an effective method of contraception or to abstain from sexual intercourse during the clinical trial and for 90 days following the last dose of the investigational new drug Subjects must be able to provide informed consent for participation in the clinical trial before any protocol-specific clinical trial procedure is performed

Exclusion Criteria:

No systemic infection requiring treatment Symptomatic brain metastases and/or progression of CNS metastases within the past 4 weeks; patients with treated CNS metastases (by surgery and/or radiation), who are neurologically stable, and who are no longer taking glucocorticoids, are eligible Subjects with autoimmune disorders, including, but not limited to: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease, ankylosing spondylitis, Hashimoto's thyroiditis, bullous pemphigus, sarcoidosis, Behçet's syndrome, vasculitis, familial Mediterranean fever, Wegener's granulomatosis or Goodpasture's syndrome Positive HIV, hepatitis B or hepatitis C antibody test Subjects who underwent allogeneic transplant New York Heart Association Grade III or IV congestive heart failure Medical, sociological or psychological conditions that may compromise compliance or participation in the clinical trial or interfere with the interpretation of the results Subjects who have taken drugs that negatively affect immune function such as systemic corticosteroids or other immunomodulatory drugs including, but not limited to, interferon-alpha, interferon-beta, interleukin-2, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept or efalizumab, within one month preceding the screening Subjects who are lactating, pregnant, or planning to become pregnant within three months of treatment completion Subjects who have received any investigational drug within the preceding four weeks of enrollment Subjects who have affected inguinal lymph nodes (metastatic process) or lack of inguinal lymph nodes (resection)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Dose Peptide Cohort	Biological: Biological: MKCC1106-MT; Cancer Vaccine, Immunotherapy
Experimental: High-Dose Peptide Cohort	Biological: Biological: MKC1106-MT; Cancer Vaccine, Immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Is to assess the safety and tolerability of MKC1106-MT regimen	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the immune response (by tetramer and ELISPOT analysis) of MKC1106-MT when administered to subjects with advanced melanoma	6 Weeks
To determine pMEL-TYR plasmid level in the blood by PCR analysis	6 Weeks
To determine target antigen expression (Melan A and tyrosinase) and beta2 microglobulin expression in the tumor tissue	6 Weeks
To document any preliminary evidence of clinical response	6 Weeks

Collaborators and Investigators

• Sponsor: Mannkind Corporation

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: May 28, 2008
• First Submitted That Met QC Criteria: May 30, 2008
• First Posted (Estimate): June 2, 2008

Study Record Updates

• Last Update Posted (Estimate): August 3, 2010
• Last Update Submitted That Met QC Criteria: August 2, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Immunotherapy, Melanoma, Cancer Vaccine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: MKC1106-MT-001