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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms

Conditions
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Leukemia, Lung Cancer, Malignant Mesothelioma, Myelodysplastic Syndromes, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Biological: WT-1 analog peptide vaccine
* Biological: incomplete Freund's adjuvant
* Biological: sargramostim
* Genetic: polymerase chain reaction
* Other: flow cytometry
* Other: immunoenzyme technique


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaccine<br>Six vaccinations of the WT-1 peptide (1.0 ml of emulsion) will be administered on weeks 0, 4, 6, 8, 10 & 12. Vaccinations will be administered subcutaneously with sites rotated among extremities. Injection sites will be pre-stimulated with Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 & -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) if they have been appropriately instructed on SQ injection administration. Patients will keep a logbook noting the time & placement of the injection. Note: during each vaccination, the Sargramostim (GM-CSF) & the vaccine emulsion will be administered to the same anatomical site. This site will be marked by the patient or treating healthcare professional by a permanent marker pen. For patients who have a clinical, molecular, or immunologic response & have not had disease progression, they may receive up to 6 more vaccinations administered approximately every month. | Biological: WT-1 analog peptide vaccine<br> <br> Biological: incomplete Freund's adjuvant<br> <br> Biological: sargramostim<br> <br> Genetic: polymerase chain reaction<br> <br> Other: flow cytometry<br> <br> Other: immunoenzyme technique<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0). | 2 years | 
| Immune Response | Immune reactivity to the peptides will be measured in the same fashion for patients with hematologic or thoracic malignancies. Immune responses will be measured by T cell proliferative response and DTH against WT-1 peptides. In patients with adequate samples, T cell gamma interferon release as measured by ELISPOT will be performed as well. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, advanced malignant mesothelioma, recurrent malignant mesothelioma, primary peritoneal cavity cancer