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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00398138
• Other study ID #: 06-085
• Secondary ID: P30CA008748P01CA
• Status: Completed
• Phase: Phase 1
• First received: November 9, 2006
• Last updated: February 2, 2016
• Start date: October 2006
• Est. completion date: June 2009

Study information

• Verified date: February 2016
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Leukemia
• Leukemia, Myeloid, Acute
• Lung Cancer
• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma
• Myelodysplastic Syndromes
• Peritoneal Neoplasms
• Preleukemia
• Primary Peritoneal Cavity Cancer
• Syndrome

Intervention

Biological:
• WT-1 analog peptide vaccine

• incomplete Freund's adjuvant

• sargramostim

Genetic:
• polymerase chain reaction

Other:
• flow cytometry

• immunoenzyme technique

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Innovive Pharmaceuticals, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva V, Zhang R, Wolchok JD, Yuan J, Pinilla-Ibarz J, Berman E, Weiss M, Jurcic J, Frattini MG, Scheinberg DA. Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell r — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0).	2 years	Yes
Primary	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	No

External Links

•   Memorial Sloan Kettering Cancer Center