Vaccine Therapy and GM-CSF in Treating Patients With Recurrent or Metastatic Melanoma

Randomized Phase II Trial of Autologous Vaccines Consisting of Adjuvant GM-CSF Plus Proliferating Tumor Cells Versus GM-CSF Plus Dendritic Cells Loaded With Proliferating Tumor Cells in Patients With Metastatic Melanoma (MAC-VAC)

RATIONALE: Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may be an effective treatment for melanoma.

PURPOSE: This randomized phase II trial is studying two different vaccine therapy regimens to compare how well they work when given together with GM-CSF in treating patients with recurrent or metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: autologous tumor cell vaccine; Biological: sargramostim; Biological: therapeutic autologous dendritic cells

Detailed Description

OBJECTIVES:

• Compare overall survival, progression-free survival, event-free survival, and failure-free survival of patients with metastatic melanoma treated with vaccine therapy comprising irradiated autologous tumor cells vs autologous dendritic cells loaded with irradiated autologous tumor cells in combination with sargramostim (GM-CSF).
• Compare the frequency of immune response based on delayed-type hypersensitivity to irradiated autologous tumor cells and serologic and cellular assays at baseline and during and after completion of autologous tumor cell-based vaccine therapy in these patients.
• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to measurable disease (yes vs no) and location of disease (distant vs regional). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irradiated autologous tumor cells subcutaneously (SC) and sargramostim (GM-CSF) SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive autologous dendritic cells loaded with irradiated autologous tumor cells SC and GM-CSF SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Hoag Cancer Institute at Hoag Memorial Hospital Presbyterian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma

  • Regionally recurrent or distant metastatic disease
• Must have an established continuously proliferating cell line expanded to about 200 million cells that is free of stromal cells and contamination

• No active CNS metastases

  • Prior treatment for brain metastases or spinal cord compression allowed
  • No clear evidence of disease progression in the CNS
  • No concurrent pharmacologic doses of corticosteroids

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 70-100% OR ECOG PS 0-1
• Platelet count > 100,000/mm³
• Hematocrit > 30%
• Creatinine < 2.0 mg/dL
• Bilirubin < 2.0 mg/dL
• Albumin > 3.0 mg/dL
• No significant hepatic or renal dysfunction
• No other invasive cancer within the past 5 years

• No active infection or other active medical condition that could be eminently life threatening, including any of the following:

  • Active blood clotting
  • Bleeding diathesis
• No ongoing transfusion requirement
• No underlying cardiac disease associated with known myocardial dysfunction
• No unstable angina related to atherosclerotic cardiovascular disease
• No known autoimmune disease
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• Prior surgery, radiotherapy, chemotherapy, biological therapy (including sargramostim [GM-CSF]), or vaccine therapy allowed
• No concurrent anticancer therapy (e.g., hormone therapy for prostate or breast cancer)
• No concurrent digoxin or other medications for the treatment of heart failure
• No concurrent immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive irradiated autologous tumor cells subcutaneously (SC) and sargramostim (GM-CSF) SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity.	Biological: autologous tumor cell vaccine; Given subcutaneously; Biological: sargramostim; Given subcutaneously
Experimental: Arm II; Patients receive autologous dendritic cells loaded with irradiated autologous tumor cells SC and GM-CSF SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity.	Biological: sargramostim; Given subcutaneously; Biological: therapeutic autologous dendritic cells; Given subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety
Overall survival, progression-free survival, event-free survival, and failure-free survival
Frequency of immune response as measured by delayed-type hypersensitivity and serologic and cellular assays at baseline and during and after completion of study treatment

Collaborators and Investigators

• Sponsor: Hoag Memorial Hospital Presbyterian
• Investigators: Study Chair: Robert O. Dillman, MD, FACP, Hoag Memorial Hospital Presbyterian

Publications and helpful links

General Publications

• Nistor GI, Dillman RO. Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial. J Transl Med. 2020 Apr 21;18(1):176. doi: 10.1186/s12967-020-02328-6.
• Dillman RO, Cornforth AN, McClay EF, Depriest C. Patient-specific dendritic cell vaccines with autologous tumor antigens in 72 patients with metastatic melanoma. Melanoma Manag. 2019 May 31;6(2):MMT20. doi: 10.2217/mmt-2018-0010.
• Dillman RO, Cornforth AN, Depriest C, McClay EF, Amatruda TT, de Leon C, Ellis RE, Mayorga C, Carbonell D, Cubellis JM. Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma. J Immunother. 2012 Oct;35(8):641-9. doi: 10.1097/CJI.0b013e31826f79c8.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 15, 2007
• First Submitted That Met QC Criteria: February 15, 2007
• First Posted (Estimate): February 19, 2007

Study Record Updates

• Last Update Posted (Estimate): January 10, 2014
• Last Update Submitted That Met QC Criteria: January 9, 2014
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• 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; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: CDR0000530026; HOAG-HCC-06-03