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

NCT ID: NCT00722098

Last Updated: 2013-07-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2012-07-31

Brief Summary

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.

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.

Conditions

Malignant Melanoma Stage IV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

DC Vaccine & Cyclophosphamide

Intervention Type: BIOLOGICAL

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.

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.

Group Type: PLACEBO_COMPARATOR

DC Vaccine & Placebo

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Cyclophosphamide (CPA); DC Vaccine ( Dendritic cell vaccine); DC Vaccine - Dendritic Cell Vaccine

Eligibility 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Fay, M.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor Institute for Immunology Research: Baylor University Medical Center

Locations

Baylor University Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

Baylor IRB #006-123

Identifier Type: -

Identifier Source: org_study_id