Chemotherapy Followed by Infusion of DMF5 Cells to Treat Metastatic Melanoma

This study has been terminated.
(study was stopped due to low accrual)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00924001
First received: June 17, 2009
Last updated: October 18, 2012
Last verified: October 2012
  Purpose

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.

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Number of Participants With an Objective Clinical Tumor Regression Response According to RECIST Criteria [ Time Frame: 44 days ] [ Designated as safety issue: No ]
    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.

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


Secondary Outcome Measures:
  • Number of Participiants With In-vivo Survival of Infused Cells [ Time Frame: 44 days ] [ Designated as safety issue: No ]
    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).


Enrollment: 1
Study Start Date: August 2007
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  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.

EXCLUSION CRITERIA:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00924001

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Rosenberg, M.D. National Cancer Institute, National Institutes of Health
  More Information

Publications:
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00924001     History of Changes
Obsolete Identifiers: NCT00537069
Other Study ID Numbers: 070210, 07-C-0210
Study First Received: June 17, 2009
Results First Received: December 22, 2011
Last Updated: October 18, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Clinical Response
Immunotherapy
Cancer
Cytokines
Adoptive Cell Therapy
Melanoma
Metastatic Melanoma

Additional relevant MeSH terms:
Melanoma
Melanoma, Experimental
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Neoplasms, Experimental
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 01, 2014