Chemotherapy Followed by Infusion of DMF5 Cells to Treat Metastatic Melanoma

NCT00924001 | Terminated Phase 1 Results DMC

• 2 other identifiers: 07021007-C-0210
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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-A201 who 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, computed tomography (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.

Conditions

Melanoma; Malignant Melanoma; Melanoma, Experimental

Keywords

Clinical Response; Immunotherapy; Cancer; Cytokines; Adoptive Cell Therapy; Melanoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With an Objective Clinical Tumor Regression Response According to RECIST Criteria

  Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% decrease in the target lesions, progression (PD) is at least a 20% increase in the target lesions or appearance of one or more new lesions, and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  44 days

• Number of Participants With Adverse Events

  Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

  44 days

Secondary Outcomes (1)

• Number of Participiants With In-vivo Survival of Infused Cells

  44 days

Study Arms (1)

Metastatic Melanoma

EXPERIMENTAL

Melanoma that has invaded deep into the skin, lymph nodes, or other parts of the body.

Drug: DMF5 Melanoma Reactive TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Interventions

DMF5 Melanoma Reactive TIL DRUG

given intravenously over 20-30 minutes (between 1 x 10\^9 and 1 x 10\^11 lymphocytes) after expansion in interleukin-2 and OKT-3

Metastatic Melanoma

Cyclophosphamide DRUG

60 mg/kg/day x 2 days intravenously

Also known as: Cytoxan, Endoxan, Neosar, Procytox, Revimmune

Metastatic Melanoma

Fludarabine DRUG

25 mg/m\^2/day intravenously x 5 days

Also known as: Fludara

Metastatic Melanoma

Aldesleukin DRUG

720,000 IU/kg/dose intravenously every 8 hours for up to 15 doses

Also known as: Proleukin

Metastatic Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic melanoma that is refractory to standard treatment including high dose aldesleukin.
• Unsuitable autologous cells for Institutional Review Board (IRB) approved Surgery Branch adoptive cell therapy studies.
• Greater than or equal to 18 years of age.
• Life expectancy of greater than three months.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document.
• Human leukocyte antigen A (HLA-A) 0201 positive.
• Willing to practice birth control during treatment and for four months after receiving the preparative regimen.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• 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.
• Serology:

You may not qualify if:

• 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.
• 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.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• 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.)
• Symptomatic central nervous system (CNS) lesions (Patients maybe eligible after treatment of their symptomatic lesions.)
• Systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms.
• Patients with a prolonged (greater than 20 pk/yrs) history of cigarette smoking or symptoms of respiratory dysfunction with pulmonary function tests (PFT's) indicating an forced expiratory volume (FEV1) less than 60 percent predicted for age.
• 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 left ventricular ejection fraction (LVEF) of less than 45 percent on cardiac evaluation (echocardiogram, multi-gated acquisition scan (MUGA), etc.) will be excluded.
• Positive allo-specific reactivity of the DMF5 cells to the patient's peripheral blood mononuclear cells (PBMC).
• Documented penicillin allergy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1084/jem.157.5.1448.

  PMID: 6189937 BACKGROUND

• 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. doi: 10.1084/jem.152.4.823.

  PMID: 6968337 BACKGROUND

• 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. doi: 10.1084/jem.161.5.1122.

  PMID: 3921652 BACKGROUND

MeSH Terms

Conditions

Melanoma; Melanoma, Experimental; Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Experimental

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Steven Rosenberg
• Organization: National Cancer Institute, National Institutes of Health

sar@mail.nih.gov

301-496-4164

Study Officials

• Steven Rosenberg, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: August 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 25, 2012
• Results First Posted: June 7, 2012

Record last verified: 2012-10

Locations

US (1)