Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome

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).

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Biological: K562/GM-CSF cell vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI); Alliance for Cancer Gene Therapy

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2007
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 4, 2006
• First Submitted That Met QC Criteria: August 4, 2006
• First Posted (Estimate): August 8, 2006

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: refractory anemia; refractory anemia with ringed sideroblasts; refractory anemia with excess blasts; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; refractory cytopenia with multilineage dysplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: J05115; P30CA006973 (U.S. NIH Grant/Contract); NA_00001530 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No