Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

Official title:

K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00361296
• Other study ID #: J05115
• Secondary ID: P30CA006973NA_00
• Status: Terminated
• Phase: Early Phase 1
• Start date: September 2007
• Est. completion date: January 2010

Study information

• Verified date: October 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: January 2010
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• K562/GM-CSF cell vaccine

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Alliance for Cancer Gene Therapy, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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