Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00361296

Purpose

RATIONALE: Vaccines made from cancer cells may help the body build an effective immune response to kill abnormal cells.

PURPOSE: This clinical trial is studying how well vaccine therapy works in treating patients with myelodysplastic syndromes (MDS).

Condition	Intervention
Myelodysplastic Syndromes	Drug: GM-K562 cell vaccine Procedure: cytogenetic analysis Procedure: flow cytometry Procedure: fluorescence in situ hybridization Procedure: immunoenzyme technique Procedure: laboratory biomarker analysis

MedlinePlus related topics: Anemia Cancer

Drug Information available for: Sargramostim Granulocyte-macrophage colony-stimulating factor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Hematologic response, defined as achieving a major response in ≥ 1 lineage as described by an erythroid increase > 2 g/dL, platelet increase of 30,000/mm³, or neutrophil increase by 100% [ Designated as safety issue: No ]
Cytogenetic response, defined as normalization of pretreatment cytogenetic abnormalities [ Designated as safety issue: No ]

Secondary Outcome Measures:

Immune response to common myeloid antigens (e.g., Wilms' tumor-1 [WT-1], survivin, or proteinase-3) as measured by Elispot assay [ Designated as safety issue: No ]
Correlation of immune response with clinical response (hematologic response, resolution of cytogenetic abnormalities, or decrease in other parameters, such as WT-1 mRNA levels) [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	August 2006
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety of GM-K562 cell vaccine in patients with myelodysplastic syndromes.
Determine the hematologic and cytogenetic response in patients treated with this vaccine.

Secondary

Determine if vaccination with GM-K562 cell vaccine can induce an immune response to common myeloid antigens (e.g., Wilms' tumor-1 [WT-1], survivin, or proteinase-3), as defined by a 30% increase from baseline in specific cytotoxic T-cells measured by Elispot assay, in patients with myelodysplastic syndromes.
Determine if immune response correlates with any clinical responses (e.g., hematologic response, resolution of cytogenetic abnormalities, or decrease in other parameters, such as WT-1 mRNA levels).

OUTLINE: This is an open-label study.

Patients receive GM-K562 cell vaccine subcutaneously once in weeks 0, 3, 6, 9, and 17 in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected periodically for correlative and biomarker studies. Samples are analyzed by cytogenetic studies, fluorescent in situ hybridization (FISH), and flow cytometry. Elispot is used to quantify cellular cytotoxic T-cell response to Wilms' tumor-1 (WT-1), survivin, and proteinase 3.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed myelodysplastic syndromes (MDS), including any of the following:
- Refractory anemia (RA)
- RA with ringed sideroblasts
- Refractory cytopenias with multilineage dysplasia (RCMD)
- RCMD with ringed sideroblasts
- RA with excess blasts 1 (5-9% blasts)
- RA with excess blasts 2 (10-19% blasts)
Must have poor-risk MDS, defined by the following:
- At least 2 lineages involved
- Unfavorable cytogenetics (i.e., abnormalities of chromosome 5 or 7, 11q23, t[6;9], trisomy 8, inv3, or multiple/complex karyotype)
- Transfusion requirement of > 2 units of packed red blood cells monthly
No chronic myelomonocytic leukemia
No transformation to acute myeloid leukemia

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Creatinine < 2.5 mg/dL
Bilirubin < 2.5 mg/dL (unless due to Gilbert's syndrome)
Room air oxygen saturation ≥ 94% at rest
Fertile patients must use effective contraception
Negative pregnancy test
No other malignancy within the past 5 years except in situ cervical cancer or adequately treated nonmelanoma skin cancer
No active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressants including, but not limited to, any of the following:
- Autoimmune hemolytic anemia
- Idiopathic thrombocytopenia purpura
- Inflammatory bowel disease
- Vasculitis
- Thyroiditis
- Rheumatic illnesses
No known HIV serum antibody positivity
No other disease requiring long-term corticosteroids or other immunosuppressants, such as severe chronic obstructive pulmonary disease or asthma

PRIOR CONCURRENT THERAPY:

At least 2 weeks since prior systemic corticosteroids or other immunosuppressants (e.g., cyclosporine, azathioprine, tacrolimus, or mycophenolate mofetil)
At least 3 weeks since prior growth factors
At least 2 months since prior azacitidine for MDS
No prior bone marrow or other organ transplantation
No concurrent cytotoxic-based therapy for MDS
No other concurrent growth factors, including epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00361296

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231
Contact: B. Douglas Smith, MD 410-614-5048 smithdo@jhmi.edu

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

B. Douglas Smith, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000491987, JHOC-J05115
Study First Received:	August 4, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00361296
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
refractory cytopenia with multilineage dysplasia

de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Myelodysplastic syndromes
Preleukemia
Anemia, Refractory
Precancerous Conditions
Refractory anemia
Hematologic Diseases

Myelodysplasia
Myelodysplastic Syndromes
Anemia
Neoplasm Metastasis
Anemia, Refractory, with Excess of Blasts
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease
Syndrome

ClinicalTrials.gov processed this record on January 16, 2009