Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma
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Purpose
This randomized phase II trial is studying how well giving vaccine therapy with or without interleukin-2 after chemotherapy and an autologous white blood cell infusion works in treating patients with metastatic melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy with interleukin-2, chemotherapy, and an autologous white blood cell infusion may be a more effective treatment for metastatic melanoma
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Melanoma Stage IV Melanoma |
Drug: cyclophosphamide Drug: fludarabine phosphate Biological: therapeutic autologous lymphocytes Procedure: in vitro-treated peripheral blood stem cell transplantation Biological: gp100 antigen Biological: MART-1 antigen Biological: incomplete Freund's adjuvant Biological: filgrastim Biological: aldesleukin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A PHASE II STUDY USING A PEPTIDE VACCINE WITH OR WITHOUT ALDESLEUKIN FOLLOWING A LYMPHODEPLETING CHEMOTHERAPY AND REINFUSION OF AUTOLOGOUS LYMPHOCYTES DEPLETED OF T REGULATORY LYMPHOCYTES IN METASTATIC MELANOMA |
- Objective clinical response (CR or PR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Presence of anti-tumor T cells [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Recovery of regulatory T cells [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Incidence of DLTs and SAEs graded according to CTCAE version 3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 58 |
| Study Start Date: | December 2005 |
| Primary Completion Date: | January 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65. Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood counts recover.
|
Drug: cyclophosphamide
Given IV
Other Names:
Drug: fludarabine phosphate
Given IV
Other Names:
Biological: therapeutic autologous lymphocytes
Given IV
Other Names:
Procedure: in vitro-treated peripheral blood stem cell transplantation
Undergo in vitro-treated peripheral blood stem cell transplantation
Other Names:
Biological: gp100 antigen
Given SC
Other Name: gp100
Biological: MART-1 antigen
Given SC
Other Names:
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
Biological: filgrastim
Given SC
Other Names:
|
|
Experimental: Arm II
Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2 treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: cyclophosphamide
Given IV
Other Names:
Drug: fludarabine phosphate
Given IV
Other Names:
Biological: therapeutic autologous lymphocytes
Given IV
Other Names:
Procedure: in vitro-treated peripheral blood stem cell transplantation
Undergo in vitro-treated peripheral blood stem cell transplantation
Other Names:
Biological: gp100 antigen
Given SC
Other Name: gp100
Biological: MART-1 antigen
Given SC
Other Names:
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
Biological: filgrastim
Given SC
Other Names:
Biological: aldesleukin
Given IV
Other Names:
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the ability of gp100 and MART-1 peptide vaccines with or without a high-dose interleukin-2 (IL-2), when administered after a nonmyeloablative, lymphodepleting preparative regimen and reinfusion of autologous CD25+ T-regulatory-depleted lymphocytes, to mediate tumor regression in patients with metastatic melanoma.
SECONDARY OBJECTIVES:
I. Determine the generation of antitumor lymphocytes and the rate of repopulation of CD25+ T-regulatory cells in patients treated with this regimen.
II. Determine the toxicity of this treatment regimen.
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65. Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood counts recover.
ARM II: Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2 treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 1-3 months.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diagnosis of metastatic melanoma
- No tumor reactive cells available for cell transfer therapy
- Measurable disease
Previously treated with interleukin-2 (IL-2) and meets 1 of the following criteria:
- No response (progressive disease)
- Recurrent disease
- HLA*0201 positive
- ECOG performance status 0 or 1
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- ALT and AST < 3 times upper limit of normal
- Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if Gilbert's disease is present)
- Creatinine ≤ 2.0 mg/dL
- Life expectancy ≥ 3 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 4 months after receiving the preparative regimen
- No active systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular, respiratory, or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, or obstructive or restrictive pulmonary disease
- No autoimmune disease (e.g., autoimmune colitis or Crohn's disease) or primary immunodeficiency disease
- No HIV positivity
- No hepatitis B or C virus positivity
- No Epstein-Barr virus negativity
Eligible to receive high-dose IL-2, as evidenced by the following:
- Patients ≥ 50 years of age must have a normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) AND LVEF ≥ 45%
- Patients with a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias must have a normal cardiac stress test AND LVEF ≥ 45%
- Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test, as evidenced by FEV 1 ≥ 60% of predicted
- At least 4 weeks since prior systemic therapy
- At least 6 weeks since prior nitrosourea therapy
- No concurrent systemic steroid therapy
- Recovered immune competence after prior chemotherapy or radiotherapy
- No prior gp100:209-217 or MART-1:27-35 peptide vaccine
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00303836 History of Changes |
| Obsolete Identifiers: | NCT00255203 |
| Other Study ID Numbers: | NCI-2012-02684, P6574, CDR0000459683 |
| Study First Received: | March 15, 2006 |
| Last Updated: | December 21, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas Cyclophosphamide Fludarabine monophosphate Fludarabine Aldesleukin Interleukin-2 Freund's Adjuvant Lenograstim |
Vidarabine 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 Adjuvants, Immunologic Analgesics, Non-Narcotic Analgesics |
ClinicalTrials.gov processed this record on May 21, 2013