Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00361296

Last Updated: 2023-03-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-01-31

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

K562/GM-CSF cell vaccine

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

Group Type: EXPERIMENTAL

K562/GM-CSF cell vaccine

Intervention Type: BIOLOGICAL

Interventions

K562/GM-CSF cell vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Cancer Gene Therapy

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

B. Douglas Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

Robinson TM, Prince GT, Thoburn C, Warlick E, Ferguson A, Kasamon YL, Borrello IM, Hess A, Smith BD. Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients. Leuk Lymphoma. 2018 Dec;59(12):2801-2811. doi: 10.1080/10428194.2018.1443449. Epub 2018 Apr 4.

Reference Type: RESULT

PMID: 29616857 (View on PubMed)

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00001530

Identifier Type: OTHER

Identifier Source: secondary_id

J05115

Identifier Type: -

Identifier Source: org_study_id