Clinical trial NCT00361296: Vaccine Therapy in Treating Patients With Myelodysplastic Syndromes
Official title: K562/GM-CSF Vaccination in Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Alliance for Cancer Gene Therapy
First posted: 2006-08-08
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Hematologic Response Rate as Assessed by Number of Participants Achieving a Major Hematologic Response
timeFrame: Baseline, week 21 post-intervention
measure: Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response
timeFrame: Week 21
Secondary outcomes:
measure: Immune Response Rate as Assessed by Number of Participants Who Exhibit Induced Immune Response to WT-1, Survivin, or Proteinase-3
timeFrame: Baseline, week 21 post-intervention
measure: Combined Immune and Clinical Response Rate
timeFrame: Week 21 post-intervention
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: B. Douglas Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.