Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

Johns Hopkins Medicine

Status and phase: Terminated; Early Phase 1

Conditions: Myelodysplastic Syndromes

Treatments: Biological: K562/GM-CSF cell vaccine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00361296

NA_00001530 (Other Identifier)

P30CA006973 (U.S. NIH Grant/Contract)

J05115

Details and patient eligibility

About

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).

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

K562/GM-CSF cell vaccine

Experimental group

Description:

Vaccinations of 1x10\^8 cells are given to participants at weeks 0, 3, 6, 9, and 17.

Treatment:

Biological: K562/GM-CSF cell vaccine