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

This study has been completed.
Sponsor:
Collaborators:
Innovive Pharmaceuticals
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00398138
First received: November 9, 2006
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Leukemia
Lung Cancer
Malignant Mesothelioma
Myelodysplastic Syndromes
Primary Peritoneal Cavity Cancer
Biological: WT-1 analog peptide vaccine
Biological: incomplete Freund's adjuvant
Biological: sargramostim
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Safety and immunogenicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Immune response as measured by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antileukemic effects [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical and molecular response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Antitumor response as measured by CT scan based on RECIST criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity as measured by NCI CTC v. 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: October 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vaccine
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 Biological: incomplete Freund's adjuvant Biological: sargramostim Genetic: polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00398138

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Innovive Pharmaceuticals
Investigators
Principal Investigator: Lee M. Krug, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00398138     History of Changes
Other Study ID Numbers: 06-085, P30CA008748, P01CA023766, MSKCC-06085
Study First Received: November 9, 2006
Last Updated: March 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lung Neoplasms
Mesothelioma
Neoplasms, Mesothelial
Myelodysplastic Syndromes
Preleukemia
Peritoneal Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Adenoma
Neoplasms, Glandular and Epithelial
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Freund's Adjuvant
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 31, 2014