Protocol Number: 07-C-0210

Title:

Phase I/II Study Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Allogeneic Tumor-Reactive Lymphocyte Cell Line DMF5 in Metastatic Melanoma

Number:

07-C-0210

Summary:

Background:

-This study will use cells called DMF5 to treat patients with metastatic melanoma (melanoma that has spread beyond the primary tumor site).

-The DMF5 cells were first obtained from a tumor of a patient with melanoma with HLA-A201 tissue type. The tumor cells were grown in the laboratory, and when the laboratory-grown cells were given back to the patient, the patient's tumors shrank dramatically. In laboratory tests, DMF5 cells were also shown to shrink mouse melanoma tumors.

Objectives:

-To determine whether preparatory chemotherapy followed by infusion of DMF5 cells is a safe and effective for shrinking melanoma tumors.

Eligibility:

-Patients with metastatic melanoma and tissue type HLA-A201who are 18 years of age or older.

Design:

-Patients have a preparatory regimen of chemotherapy with cyclophosphamide and fludarabine followed by infusion of DMF5 cells and then high-dose interleukin. The chemotherapy, interleukin and cells are given intravenously (through a vein).

-Patients have frequent blood tests to look for the side effects and response to treatment.

-Patients may be asked to have a tumor biopsy (surgical removal of a small piece of tumor tissue) to examine the effects of treatment on the immune cells in the tumor.

-Patients have a physical examination, CT of the chest, abdomen and pelvis and laboratory tests 4 to 6 weeks after treatment and then monthly to evaluate the tumor.

-The first group of patients participates in the Phase I portion of the study, called the dose escalation phase. This phase will determine the highest safe dose of DMF5 cells. There will be three dose levels of DMF5 cells, with the first patients enrolled getting the smallest dose and then increasing the dose when the preceding level has been shown to be safe.

-Patients in the Phase II portion of the study receive DMF5 cells at the highest dose found to be safe in Phase I, to test the effectiveness of the treatment.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

a. Measurable metastatic melanoma that is refractory to standard treatment including high dose aldesleukin.

b. Unsuitable autologous cells for IRB approved Surgery Branch adoptive cell therapy studies.

c. Greater than or equal to 18 years of age.

d. Life expectancy of greater than three months.

e. Willing to sign a durable power of attorney.

f. Able to understand and sign the Informed Consent Document.

g. HLA-A 0201 positive.

h. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.

i. Clinical performance status of ECOG 0 or 1.

j. Hematology:

-Absolute neutrophil count greater than 1000/mm(3) without support of filgrastim.

-WBC greater than 3000/mm(3).

-Hemoglobin greater than 8.0 g/dl.

-Platelet count greater than 100,000/mm(3).

k. Serology:

-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 and hepatitis C antibody unless antigen negative.

-Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

l. Chemistry:

-Serum ALT/AST less than three times the upper limit of normal.

-Serum creatinine less than or equal to 1.6 mg/dl.

-Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

m. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

n. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to decline.

o. Patients who have previously received MDX-010 must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

a. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

b. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

c. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

d. Opportunistic infections (The experimental treatment being evaluated in his protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

e. Symptomatic CNS lesions (Patients maybe eligible after treatment of their symptomatic lesions.)

f. Systemic steroid therapy.

g. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

h. History of coronary revascularization or ischemic symptoms.

i. Patients with a prolonged (greater than 20 pk/yrs) history of cigarette smoking or symptoms of respiratory dysfunction with PFT's indicating an FEV1 less than 60 percent predicted for age.

j. Patients with a history of clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, heart block or greater than or equal to age 60 with an LEVF of less than 45 percent on cardiac evaluation (echocardiogram, MUGA, etc.) will be excluded.

k. Positive allo-specific reactivity of the DMF5 cells to the patient's PBMC.

l. Documented penicillin allergy.

Special Instructions:

Currently Not Provided

Keywords:

Clinical Response

Immunotherapy

Cancer

Cytokines

Adoptive Cell Therapy

Recruitment Keyword(s):

Melanoma

Metastatic Melanoma

Condition(s):

Melanoma

Malignant Melanoma

Melanoma, Experimental

Investigational Drug(s):

DME5 Melanoma Reactive TIL

Investigational Device(s):

None

Intervention(s):

Drug: DME5 Melanoma Reactive TIL

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Aldesleukin

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

Mills CD, North RJ. Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient. Inhibition by suppressor T cells. J Exp Med. 1983 May 1;157(5):1448-60.

Fernandez-Cruz E, Woda BA, Feldman JD. Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes. J Exp Med. 1980 Oct 1;152(4):823-41.

Greenberg PD, Kern DE, Cheever MA. Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2- T cells. Tumor eradication does not require participation of cytotoxic T cells. J Exp Med. 1985 May 1;161(5):1122-34.

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