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

November 9, 2006
March 6, 2013
October 2006
June 2009   (final data collection date for primary outcome measure)
  • 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 ]
  • Safety and immunogenicity
  • Immune response as measured by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT
Complete list of historical versions of study NCT00398138 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Antileukemic effects
  • Clinical and molecular response
  • Antitumor response by CT scan based on RECIST criteria
  • Toxicity as measured by NCI CTC v. 3.0
Not Provided
Not Provided
 
Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma
Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms

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.

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.

Interventional
Not Provided
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
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.
Interventions:
  • Biological: WT-1 analog peptide vaccine
  • Biological: incomplete Freund's adjuvant
  • Biological: sargramostim
  • Genetic: polymerase chain reaction
  • Other: flow cytometry
  • Other: immunoenzyme technique
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 responses in patients with complete remission from acute myeloid leukemia. Blood. 2010 Jul 15;116(2):171-9. doi: 10.1182/blood-2009-10-250993. Epub 2010 Apr 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
June 2009
June 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00398138
06-085, P30CA008748, P01CA023766, MSKCC-06085
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
  • National Cancer Institute (NCI)
  • Innovive Pharmaceuticals
Principal Investigator: Lee M. Krug, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP