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Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

This experiment will test the safety and effectiveness of a treatment for metastatic melanoma in which certain lymphocytes (a type of white blood cell) are taken from the patient, grown in the laboratory, and returned after the patient's immune system has been weakened with immune-suppressing drugs. Some patients will also receive interleukin-2, a drug that may enhance the activity of the re-infused lymphocytes.

Patients with metastatic melanoma (melanoma whose tumor has spread) who have been treated unsuccessfully with gp100 vaccination may participate in this study. They will undergo apheresis or a tumor biopsy, or both, to collect lymphocytes. In apheresis, whole blood is drawn through a needle in the arm. A machine separates the blood components and removes the white cells. The rest of the blood is returned through a needle in the other arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue. We will find the best cells to fight the melanoma from cells obtained from the pheresis or biopsy. We will take these and grow them in larger numbers in the laboratory. These are called "cloned cells" because we grow a lot of cells that are exactly like the best melanoma fighting cells we started with.

Several weeks before we weaken the immune system and give the "cloned cells", additional lymphocytes are collected after patients receive injections of G-CSF every day for five days. This drug stimulates white cell production, permitting as many cells as possible to be obtained during collection. These white cells will be frozen in the laboratory and will only be given back to the patient if their immune system does not completely recover from the chemotherapy drugs used to suppress the immune system.

Seven days before the "cloned cells" are re-infused, the patient is admitted to the hospital and a catheter (small tube) is placed in a large vein in the chest or neck. Two drugs, cyclophosphamide and fludarabine, are given through the tube. These drugs suppress the immune system so that it will not interfere with the work of the reinfused lymphocytes. The lymphocytes are then given through the catheter over a 30-minute period. After the infusion, patients who receive IL-2 will be given the drug over a 15-minute period every 8 hours for up to 5 days. Fourteen to 21 days after this, the patient will be given a second infusion of "cloned cells".

Blood and tissue samples will be taken before and during the study to evaluate the size of the tumor and response to treatment. If, 3 to 5 weeks after therapy is completed, scans and x-rays of the patient's tumor show that is has stabilized or shrunk, the cell treatment, except for chemotherapy, may be repeated two more times.

Condition Treatment or Intervention Phase
Melanoma
Neoplasm Metastasis
 Drug: gp100:209-217 (210M)
 Drug: Montanide ISA-51
 Drug: IL-2
 Drug: Retroviral Vector PG13/LNC8
 Drug: OKT3
 Drug: MART-1:26-35(27L)
Phase II

MedlinePlus related topics:  Cancer;   Cancer Alternative Therapy;   Melanoma

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: Treatment of Patients with Metastatic Melanoma Using Cloned Lymphocytes Following the Administration of a Non-Myeloablative but Lymphocyte Depleting Regimen

Further Study Details: 

Expected Total Enrollment:  220

Study start: August 26, 1999

Patients with metastatic melanoma who are HIV and Hepatitis B negative and who have previously progressed after receiving standard therapy will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with shared antigens on their tumors. This study will evaluate the toxicity, immunologic effects and potential therapeutic role of this treatment.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA
Patients must have evaluable metastatic melanoma that is refractory to standard therapy.
Age greater than or equal to 16 years.
Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
Clinical performance status of ECOG 0, 1 at entry to the trial and at the time of chemotherapy induction.
Absolute neutrophil count greater than 1000/mm(3).
Platelet count greater than 100,000/mm(3).
Hemoglobin greater than 8.0 g/dl.
Serum ALT/AST less than two times the upper limit of normal.
Serum creatinine less than or equal to 1.6 mg/dl.
Total bilirubin less than or equal to 1.6 mg/dl, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
More than four weeks must have elapsed since any prior therapy at the time the patient receives the preparative regimen.
Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
Life expectancy of greater than three months.
No steroid therapy required.
Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
Seronegative for hepatitis B antigen.
Patients to receive high dose IL-2 must have no active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system.
Patients who will receive high doseIL-2 as part of the phase I portion of this study or who will be randomized must be eligible to receive high dose IL-2.
Any patient receiving IL-2 must sign a durable power of attorney.

Location and Contact Information


Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Rosenberg SA. Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer. J Clin Oncol. 1992 Feb;10(2):180-99. Review. No abstract available.

Schwartzentruber DJ, Topalian SL, Mancini M, Rosenberg SA. Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IFN-gamma by human tumor-infiltrating lymphocytes after autologous tumor stimulation. J Immunol. 1991 May 15;146(10):3674-81.

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

Study ID Numbers:  990158; 99-C-0158
Record last reviewed:  August 1, 2004
Last Updated:  August 1, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001832
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-29
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