Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Melanoma

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00003552

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy plus peripheral stem cell transplantation in treating patients with metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: allogeneic lymphocytes Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: fludarabine	Phase 1/Phase 2

Detailed Description

OBJECTIVES: I. Identify an antitumor effect of allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with metastatic melanoma.

Evaluate the safety and toxicity of a nonmyeloablative, low intensity, preparative regimen followed by an HLA-matched allogeneic PBSCT in these patients.
Monitor engraftment by measuring donor-recipient chimerism in lymphoid and myeloid lineages in these patients.
Investigate the relationship between donor-host chimerism and the incidence of acute and chronic graft-versus-host disease in this patient population.
Investigate the effect of lymphocyte infusions on donor-host chimerism in this patient population.
Determine disease-free survival, overall survival, and mortality from the procedure or tumor progression in this patient population.

PROTOCOL OUTLINE: This is a dose-escalation study of a conditioning regimen. Patients receive 1 of 3 dose levels of chemotherapy prior to peripheral blood progenitor cell (PBPC) transplantation. Patients at dose level 1 receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes daily on days -5 to -1. Patients at dose level 2 receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2. Patients at dose level 3 receive cyclophosphamide IV over 1 hour daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2.

Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may be repeated on days 1 and 2 if deemed necessary.

Patients with progressive disease on days 15-30, day 60, or day 100, without graft-versus-host disease, receive infusion(s) of donor lymphocytes. Further donor lymphocyte infusions after day 100 may be given at the discretion of the attending physician.

Patients are followed every 2 months for 6 months, every 3 months for the next 2 years, and then every 6 months until year 5 posttransplantation.

PROJECTED ACCRUAL:

A total of 40 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Phase I/II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation Followed by Allogeneic T-cell Infusion as Adoptive Immunotherapy in Patients With Metastatic Melanoma

Study Start Date :

Jan 1, 1999

Actual Study Completion Date :

Oct 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Histologically confirmed metastatic melanoma not amenable to complete surgical resection and progressive despite immunotherapy and/or chemotherapy Bidimensionally evaluable clinically or radiographically HLA 6/6 or 5/6 matched sibling donor available No CNS metastases --Prior/Concurrent Therapy-- See Disease Characteristics At least 30 days since prior treatment for melanoma --Patient Characteristics-- Age: 18 to 60 Performance status: ECOG 0-1 Life expectancy: At least 3 months Hematopoietic: Not specified Hepatic: Bilirubin no greater than 4 mg/dL Transaminases no greater than 3 times upper limit of normal Renal: Creatinine no greater than 2.5 mg/dL Cardiovascular: Left ventricular ejection fraction greater than 40% Pulmonary: DLCO greater than 65% of predicted Other: HIV negative No major organ dysfunction precluding transplantation No other malignancies except basal cell or squamous cell skin cancer No psychiatric disorder or mental deficiency that would preclude study Not pregnant or nursing