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Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT00361296
Recruitment Status : Terminated (Loss of funding)
First Posted : August 8, 2006
Results First Posted : November 16, 2018
Last Update Posted : November 16, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Alliance for Cancer Gene Therapy
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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).


Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Biological: K562/GM-CSF cell vaccine Early Phase 1

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  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome
Actual Study Start Date : September 2007
Actual Primary Completion Date : October 2009
Actual Study Completion Date : January 2010


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



Primary Outcome Measures :
  1. Hematologic Response Rate as Assessed by Number of Participants Achieving a Major Hematologic Response [ Time Frame: Baseline, week 21 post-intervention ]
    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.

  2. Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response [ Time Frame: Week 21 ]
    Cytogenetic response is defined as normalization of pretreatment cytogenetic abnormalities.


Secondary Outcome Measures :
  1. Immune Response Rate as Assessed by Number of Participants Who Exhibit Induced Immune Response to WT-1, Survivin, or Proteinase-3 [ Time Frame: Baseline, week 21 post-intervention ]
    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.

  2. Combined Immune and Clinical Response Rate [ Time Frame: Week 21 post-intervention ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00361296


Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Alliance for Cancer Gene Therapy
Investigators
Principal Investigator: B. Douglas Smith, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications of Results:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00361296     History of Changes
Other Study ID Numbers: J05115
P30CA006973 ( U.S. NIH Grant/Contract )
NA_00001530 ( Other Identifier: JHMIRB )
First Posted: August 8, 2006    Key Record Dates
Results First Posted: November 16, 2018
Last Update Posted: November 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
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

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs