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Chemotherapy Followed by Infusion of DMF5 Cells to Treat Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT00924001
Recruitment Status : Terminated (study was stopped due to low accrual)
First Posted : June 18, 2009
Results First Posted : June 7, 2012
Last Update Posted : October 25, 2012
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:


  • 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.


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


-Patients with metastatic melanoma and tissue type HLA-A201 who are 18 years of age or older.


  • 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.

Condition or disease Intervention/treatment Phase
Melanoma Malignant Melanoma Melanoma, Experimental Drug: DMF5 Melanoma Reactive TIL Drug: Cyclophosphamide Drug: Fludarabine Drug: Aldesleukin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : August 2007
Actual Primary Completion Date : October 2010
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Metastatic Melanoma
Melanoma that has invaded deep into the skin, lymph nodes, or other parts of the body.
Drug: DMF5 Melanoma Reactive TIL
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

Drug: Cyclophosphamide
60 mg/kg/day x 2 days intravenously
Other Names:
  • Cytoxan
  • Endoxan
  • Neosar
  • Procytox
  • Revimmune

Drug: Fludarabine
25 mg/m^2/day intravenously x 5 days
Other Name: Fludara

Drug: Aldesleukin
720,000 IU/kg/dose intravenously every 8 hours for up to 15 doses
Other Name: Proleukin

Primary Outcome Measures :
  1. Number of Participants With an Objective Clinical Tumor Regression Response According to RECIST Criteria [ Time Frame: 44 days ]
    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.

  2. Number of Participants With Adverse Events [ Time Frame: 44 days ]
    Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Secondary Outcome Measures :
  1. Number of Participiants With In-vivo Survival of Infused Cells [ Time Frame: 44 days ]
    In-vivo survival of infused cells is determined by analysis of the sequence of the variable region of the T cell receptor or flow cytometry (FACS).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. Measurable metastatic melanoma that is refractory to standard treatment including high dose aldesleukin.
  2. Unsuitable autologous cells for Institutional Review Board (IRB) approved Surgery Branch adoptive cell therapy studies.
  3. Greater than or equal to 18 years of age.
  4. Life expectancy of greater than three months.
  5. Willing to sign a durable power of attorney.
  6. Able to understand and sign the Informed Consent Document.
  7. Human leukocyte antigen A (HLA-A) 0201 positive.
  8. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.
  9. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
  10. 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.
  11. Serology:

    • Seronegative for human immunodeficiency virus (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.
  12. Chemistry:

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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.
  13. 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).
  14. Six weeks must have elapsed since prior Ipilimumab (MDX-010) therapy to allow antibody levels to decline.
  15. Patients who have previously received MDX-010 must have a normal colonoscopy with normal colonic biopsies.


  1. 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.
  2. 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.
  3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  4. 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.)
  5. Symptomatic central nervous system (CNS) lesions (Patients maybe eligible after treatment of their symptomatic lesions.)
  6. Systemic steroid therapy.
  7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  8. History of coronary revascularization or ischemic symptoms.
  9. 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.
  10. 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.
  11. Positive allo-specific reactivity of the DMF5 cells to the patient's peripheral blood mononuclear cells (PBMC).
  12. Documented penicillin allergy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00924001

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Steven Rosenberg, M.D. National Cancer Institute, National Institutes of Health
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Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00924001    
Obsolete Identifiers: NCT00537069
Other Study ID Numbers: 070210
First Posted: June 18, 2009    Key Record Dates
Results First Posted: June 7, 2012
Last Update Posted: October 25, 2012
Last Verified: October 2012
Keywords provided by National Institutes of Health Clinical Center (CC):
Clinical Response
Adoptive Cell Therapy
Metastatic Melanoma
Additional relevant MeSH terms:
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Melanoma, Experimental
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Experimental
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents