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Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma

Saturday, March 1, 2008

Clinical Trial Phase: Phase 1 | Start Date: October 2006
Overall Status: Recruiting
Estimated Enrollment: 20

Rationale

Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Giving vaccine therapy together with GM-CSF may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects of vaccine therapy and GM-CSF in treating patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma.
Study Type: Interventional
Study Design: Treatment
Detailed Clinical Trial Description

OBJECTIVES: Primary – Determine the safety and immunogenicity of the Wilms tumor-1 analog peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma.
Secondary – Determine the antitumor effects of this vaccine in these patients.

OUTLINE: This is a pilot study. Patients are stratified according to disease type (acute myeloid leukemia [AML] or myelodysplastic syndromes [MDS] vs non-small cell lung cancer or mesothelioma).
Patients receive vaccine comprising Wilms-tumor 1 (WT-1) analog peptide emulsified in Montanide ISA-51 subcutaneously (SC) once in weeks 0, 4, 6, 8, 10, and 12 and sargramostim (GM-CSF) SC twice in weeks 0, 4, 6, 8, 10, and 12 (on the day of and 2 days prior to each vaccination). Patients who have an immunologic response and have no disease progression may receive up to 6 more vaccinations approximately 1 month apart.
Blood samples are collected at baseline, week 8, and week 14. Samples are examined by polymerase chain reaction (PCR) to measure levels of WT-1 and by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT to measure immune response.
Bone marrow samples are collected from patients with AML or MDS at baseline and week 14.

Samples are examined by PCR to measure levels of WT-1 and by multiparameter flow cytometry to measure residual disease.

Intervention(s)

• Drug: WT-1 analog peptide vaccine
• Drug: incomplete Freund’s adjuvant
• Drug: sargramostim
• Procedure: diagnostic procedure
• Procedure: flow cytometry
• Procedure: immunoenzyme technique
• Procedure: non-specific immune-modulator therapy
• Procedure: non-tumor cell-derivative vaccine therapy
• Procedure: polymerase chain reaction

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary

• Safety and immunogenicity
• Immune response as measured by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT

Secondary

• Antileukemic effects
• Clinical and molecular response
• Antitumor response as measured by CT scan based on RECIST criteria
• Toxicity as measured by NCI CTC v. 3.0

DISEASE CHARACTERISTICS

• Cytologically or histologically confirmed diagnosis of 1 of the following:
• Acute myeloid leukemia, meeting the following criteria:
• Documented Wilms tumor-1 (WT-1)-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease with real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR)
• Completed induction chemotherapy, achieved clinical remission, and completed postremission therapy OR achieved clinical remission and have no plans for further postremission chemotherapy (≥ 65 years of age)
• Myelodysplastic syndromes, meeting the following criteria:
  • Documented WT-1-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease by RQ-PCR
  • International Prognostic Scoring System (IPSS) score of ≥ Int-2
  • Not a candidate for cytotoxic chemotherapy
• Non-small cell lung cancer, meeting the following criteria:
  • Positive tumor staining for WT-1 in > 10% of cells
  • Stage III or IV disease
  • Completed chemotherapy, surgery, and/or radiotherapy
• Mesothelioma, meeting the following criteria:
  • Positive tumor staining for WT-1 in > 10% of cells
  • Unresectable or relapsed disease
  • Chemo-naive or received 1 prior chemotherapy regimen
  • Malignant pleural mesothelioma or peritoneal mesothelioma
  • No leptomeningeal disease
  • No CNS involvement

PATIENT CHARACTERISTICS

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count > 50,000/mm³ (except for myelodysplastic syndromes where parameter is >
• 20,000/mm³ and not transfusion dependent)
• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
• No serious unstable medical illness

PRIOR CONCURRENT THERAPY

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy or radiotherapy
• No concurrent systemic corticosteroids

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Memorial Sloan-Kettering Cancer Center
Memorial Sloan – Kettering Cancer Center
New York New York 10021 United States

Overall Clinical Trial Officials and Contacts
Lee M. Krug, MD Principal Investigator Memorial Sloan-Kettering Cancer Center

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00398138
Study ID Number: CDR0000513334
ClinicalTrials.gov Identifier: NCT00398138

Labels: ClinicalTrial

posted by Your Attorney at 3:40 PM
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