Comparison Study of Dendritic Cell Vaccine With and Without Cyclophosphamide to Treat Stage IV Melanoma Patients

This study has been terminated.
(Early termination due to lesser accrual, and data analysis not done.)
Sponsor:
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00722098
First received: July 23, 2008
Last updated: July 5, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to determine whether the combination of chemotherapy (Cyclophosphamide) and CD34-DC vaccines results in the improved rate of clinical responses for stage IV melanoma patients.


Condition Intervention Phase
Malignant Melanoma Stage IV
Biological: DC Vaccine & Cyclophosphamide
Biological: DC Vaccine & Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Melanoma Peptide-Loaded Dendritic Cell Vaccine in HLA-A*0201 Patients With Stage IV Melanoma: A Phase II Randomized Trial to Compare Vaccination With and Without Cyclophosphamide Treatment.

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • Induction of melanoma-specific CD8+T Cell Immunity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of objective clinical responses. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: June 2008
Study Completion Date: July 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DC Vaccine & Cyclophosphamide

Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities.

Patients will receive either CPA 300mg/m2 for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.

Biological: DC Vaccine & Cyclophosphamide

Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities.

Patients will receive either CPA 300mg/m2 for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.

Other Names:
  • Cyclophosphamide (CPA)
  • DC Vaccine ( Dendritic cell vaccine)
Placebo Comparator: DC Vaccine & Placebo

Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities.

Patients will receive saline for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.

Biological: DC Vaccine & Placebo

Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities.

Patients will receive saline for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.

Other Name: DC Vaccine - Dendritic Cell Vaccine

Detailed Description:

Vaccination of patients with metastatic melanoma using ex vivo generated dendritic cells (DCs) loaded with tumor-associated antigen(s) have been shown to induce tumor-specific immunity against melanoma antigens measured by in vitro assays and, in some cases, tumor regression. At the present time, the numbers of recorded patients with metastatic melanoma who have been treated with DC vaccinations are too small to predict with certainty the future of overall therapeutic value of DC vaccinations in the management of patients with metastatic melanoma. The purpose of this study is to gather data on feasibility and efficacy of novel combination therapy of CPA and a DC vaccine outlined in this protocol to treat metastatic melanoma.

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Biopsy-proven metastatic melanoma, Stages M1a, M1b, M1c
  2. HLA-A*0201 phenotype
  3. Age: 21-75 years
  4. ECOG performance status 0-1
  5. Measurable metastatic melanoma lesions by physical examination or radiographs or scans.
  6. Adequate marrow function:

    • White count ≥ 4,000/microliter: Subjects who have recently completed chemotherapy will be allowed study entry with White count ≥ 3,500/microliter
    • Hemoglobin ≥ 10.0 gm: Subjects who have recently completed chemotherapy will be allowed study entry with Hemoglobin ≥ 9.0 gm.
    • Platelets ≥ 100,000/microliter
  7. Adequate hepatic function:

    • Bilirubin ≤ 1.5/mg/dL
    • Alkaline phosphatase ≤ 5 times the upper limit of normal
    • SGOT ≤ 5 times the upper limit of normal
    • SGPT ≤ 5 times the upper limit of normal
  8. Adequate renal function:

    • Serum creatinine ≤ 1.5/mg/dL
  9. No active CNS metastatic disease at screening.

    • Patients with a history of CNS melanoma lesions must have had lesions resected by surgery and/or gamma knife irradiation at least 3 months prior to study entry.
    • The total number of CNS lesions at diagnosis should not have exceeded 3.
  10. Written informed consent

Exclusion Criteria:

  1. Patients who have received > 8 cycles of cytotoxic chemotherapy or metastatic melanoma
  2. Patients who have received any chemotherapy < 4 weeks before the beginning of the trial
  3. Patients who have received interferon alpha (IFNα-2b) or sargramostim (GM-CSF) < 4 weeks before the beginning of the trial
  4. Patients who have received high-dose interleukin-2 (IL-2) < 4 weeks before the beginning of the trial
  5. Patients that have been diagnosed with more than 3 CNS melanoma lesions.
  6. Patients that have been diagnosed with more than 5 hepatic metastases or any hepatic metastasis > 5 cm.
  7. Baseline serum LDH > 1.1 times the upper limit of normal
  8. Patients who are HIV+ (HIV patients are often profoundly immunodeficient because of the viral infection and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. Furthermore, the safety of collecting DCs, loading them with antigen and re-infusing these cells to HIV+ patients has not yet been determined.)
  9. Pregnancy (Pregnancy is associated with considerable immunosuppression 70 and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. In addition, the safety and tolerability of cell body-loaded DC given subcutaneously is entirely unknown.)
  10. Patients who have received corticosteroids or other immunosuppressive agents < 4 weeks before beginning the trial
  11. Patients with active asthma and/or on treatment for asthma
  12. Patients with angina pectoris
  13. Patients with congestive heart failure
  14. Patients with a history of autoimmune disease including lupus erythematosus, rheumatoid arthritis or thyroiditis
  15. Patients with active infections including viral hepatitis
  16. Patients with a history of neoplastic disease other than melanoma < 5 years prior to entry on the trial except for patients with carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin. Patients who have any of these two types of cancer and melanoma can be included.
  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: NCT00722098

Locations
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75204
Sponsors and Collaborators
Baylor Research Institute
Investigators
Principal Investigator: Joseph Fay, M.D. Baylor Institute for Immunology Research: Baylor University Medical Center
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00722098     History of Changes
Other Study ID Numbers: Baylor IRB #006-123
Study First Received: July 23, 2008
Last Updated: July 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
Melanoma
Dendritic Cell
Vaccine
Immunotherapy
Cyclophosphamide

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 19, 2014