Clinical trial NCT00398138: Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma
Official title: Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lung Cancer
Malignant Mesothelioma
Myelodysplastic Syndromes
Primary Peritoneal Cavity Cancer
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Innovive Pharmaceuticals
First posted: 2006-11-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Safety
timeFrame: 2 years
measure: Immune Response
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lee M. Krug, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.