- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01339663
Vaccine Therapy Following Therapeutic Autologous Lymphocytes and Cyclophosphamide in Treating Patients With Metastatic Melanoma
Phase I Study To Evaluate The Use Of Autologous T- Antigen-Presenting Cells (T-APC) To Enhance The Persistence Of Adoptively Transferred CD8+ Antigen-Specific T Cells (CTL) Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Assess the safety and toxicity of T-APC vaccination following adoptive T cell therapy.
II. Evaluate the functional and numeric in vivo persistence of adoptively transferred cytotoxic t lymphocytes (CTL) followed by T-APC vaccination.
SECONDARY OBJECTIVES:
I. Evaluate the antitumor effect of adoptive T cell therapy followed by T-APC vaccination.
OUTLINE : This is a dose-escalation study of T-APC vaccine.
INFUSION I: Patients receive high-dose cyclophosphamide intravenously (IV) on days -4 and -3 and low-dose aldesleukin (IL-2) subcutaneously (SC) twice daily (BID) on days 0-14. Patients also receive CTL IV on day 0.
INFUSION II: Beginning 6-48 hours later, patients receive high-dose cyclophosphamide, low-dose IL-2, and CTL as in Infusion I. Patients also receive T-APC vaccine IV within 18-36 hours following CTL infusion and in week 4, and IL-2 SC BID on days 0-14 following second T-APC vaccination.
After completion of study treatment, patients are followed up for 8 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
- Tumor expression of melanocyte differentiation antigen (MDA: MART-1 = 2+ staining or > 25%) by immunohistochemistry (IHC)
- Expression of human leukocyte antigen (HLA)-A201
- Zubrod performance status of '0-1' at the time of treatment
- Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
- Normal cardiac stress test will be required for all patients with any history of cardiac disease
Exclusion Criteria:
- Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
- Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min
- Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal
- Bilirubin > 1.6 mg/dL
- Prothrombin time > 1.5 x control
- Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for hemoglobin [Hgb]) < 75% will be excluded
- Congestive heart failure
- Clinically significant hypotension
- Symptoms of coronary artery disease
- Presence of cardiac arrhythmias on electrocardiograph (EKG) requiring drug therapy
- Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA])
- Symptomatic central nervous system metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment
- Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
- Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
- Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives
- Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy
- Current treatment with steroids
- Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
- Patients for whom we are unable to generate MART-1 specific T cells
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (dose-escalation, T-APC boost, CTL)
INFUSION I: Patients receive high-dose cyclophosphamide IV on day days -4 and -3 and low-dose IL-2 SC BID on days 0-14. Patients also receive CTL IV on day 0. INFUSION II: Beginning 6-48 hours later, patients receive high-dose cyclophosphamide, low-dose IL-2, and CTL as in Infusion I. Patients also receive T-APC vaccine IV within 18-36 hours following CTL infusion and in week 4, and IL-2 SC BID on days 0-14 following second T-APC vaccination. |
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Correlative studies
Other Names:
Correlative studies
Other Names:
Given SC
Other Names:
Receive T-APC via IV
Other Names:
Receive adoptively transferred CD8+ antigen-specific T cell clones via IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-related dose limiting toxicity (DLT) as defined by Grade 3 or greater unexpected toxicity by the NCI Common Toxicity Criteria (CTC) v4.0
Time Frame: Up to 8 weeks after the T cell infusion
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Assessed at the maximum tolerated dose (MTD) or dose level immediately below the dose level for which the incidence of DLT was less than 35%.
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Up to 8 weeks after the T cell infusion
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In vivo persistence of adoptively transferred T cells
Time Frame: At 4 weeks
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Assessed by intrapatient comparison between the first (without T-APC) and second (with T-APC) CTL infusion.
Descriptive statistics will be applied and t-tests of intrapatient in vivo T cell persistence between the two Infusions will be determined.
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At 4 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Clinical response
Time Frame: Up to 8 weeks after second dose
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Up to 8 weeks after second dose
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Sylvia Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Aldesleukin
- Cyclophosphamide
- Vaccines
- Interleukin-2
Other Study ID Numbers
- 2481.00
- K12CA076930 (U.S. NIH Grant/Contract)
- NCI-2011-00383 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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