Myelodysplastic Syndromes
Conditions
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
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.
Interventions
BIOLOGICALK562/GM-CSF cell vaccine
Sponsors
National Cancer Institute (NCI)
Alliance for Cancer Gene Therapy
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Response Rate as Assessed by Number of Participants Achieving a Major Hematologic Response | 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. |
| Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response | Week 21 | Cytogenetic response is defined as normalization of pretreatment cytogenetic abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response Rate as Assessed by Number of Participants Who Exhibit Induced Immune Response to WT-1, Survivin, or Proteinase-3 | 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. |
| Combined Immune and Clinical Response Rate | 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. |
Countries
United States
Participant flow
Pre-assignment details
2 participants were screen failures. 2 additional participants were removed from study by physician decision prior to receiving protocol intervention, so they never started the study.
Participants by arm
| Arm | Count |
|---|---|
| K562/GM-CSF Cell Vaccine Vaccinations of 1x10\^8 cells are given to participants at weeks 0, 3, 6, 9, and 17.
K562/GM-CSF cell vaccine | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | K562/GM-CSF Cell Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response
Cytogenetic response is defined as normalization of pretreatment cytogenetic abnormalities.
Time frame: Week 21
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K562/GM-CSF Cell Vaccine | Cytogenetic Response Rate as Assessed by Number of Participants Achieving a Cytogenetic Response | 0 Participants |
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.
Time frame: Baseline, week 21 post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K562/GM-CSF Cell Vaccine | Hematologic Response Rate as Assessed by Number of Participants Achieving a Major Hematologic Response | 1 Participants |
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.
Time frame: Week 21 post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K562/GM-CSF Cell Vaccine | Combined Immune and Clinical Response Rate | 0 Participants |
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.
Time frame: Baseline, week 21 post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K562/GM-CSF Cell Vaccine | Immune Response Rate as Assessed by Number of Participants Who Exhibit Induced Immune Response to WT-1, Survivin, or Proteinase-3 | 0 Participants |