Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. 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

1. Determine the antitumor effects of this vaccine in these patients.

Entry Criteria

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

Prior/Concurrent Therapy:

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

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

Expected Enrollment

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

Outcomes

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

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

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.

Maslak PG, Dao T, Krug LM, et al.: Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood 116 (2): 171-9, 2010.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Lee Krug, MD, Principal investigator		Ph: 212-639-8420; 800-525-2225

Registry Information
Official Title		Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients with Thoracic and Myeloid Neoplasms
Trial Start Date		2006-10-03
Trial Completion Date		2008-11-11
Registered in ClinicalTrials.gov		NCT00398138
Date Submitted to PDQ		2006-10-09
Information Last Verified		2008-12-14
NCI Grant/Contract Number		CA08748, CA23766

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