Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

Study Overview
=================
Brief Summary
-----------------
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).

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.

Official Title
-----------------
K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome

Conditions
-----------------
Myelodysplastic Syndromes

Intervention / Treatment
-----------------
* Biological: K562/GM-CSF cell vaccine


Participation Criteria
=================
Eligibility 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: K562/GM-CSF cell vaccine<br>Vaccinations of 1x10^8 cells are given to participants at weeks 0, 3, 6, 9, and 17. | Biological: K562/GM-CSF cell vaccine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic Response Rate as Assessed by Number of Participants Achieving a Major Hematologic Response | A major hematologic response is defined as any of the following: hemoglobin increase >= 2 g/dL from baseline; platelet increase >= 30k/mcL from baseline; or neutrophil increase >= 100% or >= 500/mcL from baseline. | Baseline, week 21 post-intervention | 
| Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response | Cytogenetic response is defined as normalization of pretreatment cytogenetic abnormalities. | Week 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response Rate as Assessed by Number of Participants Who Exhibit Induced Immune Response to WT-1, Survivin, or Proteinase-3 | Immune response to WT-1, survivin, or proteinase-3 as defined by a 30% increase from baseline in cytotoxic T cells measured by Elispot analysis. | Baseline, week 21 post-intervention | 
| Combined Immune and Clinical Response Rate | Number of participants who exhibited both an immune response as defined by Outcome 3 and a hematologic or cytogenetic response as defined by Outcomes 1 and 2, respectively. | Week 21 post-intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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