Leukemia, Lung Cancer, Malignant Mesothelioma, Myelodysplastic Syndromes, Primary Peritoneal Cavity Cancer
Conditions
Keywords
adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, advanced malignant mesothelioma, recurrent malignant mesothelioma, primary peritoneal cavity cancer
Brief summary
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Giving vaccine therapy together with GM-CSF may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects of vaccine therapy and GM-CSF in treating patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma.
Detailed description
OBJECTIVES: Primary * Determine the safety and immunogenicity of the Wilms tumor-1 analog peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma. Secondary * Determine the antitumor effects of this vaccine in these patients. OUTLINE: This is a pilot study. Patients are stratified according to disease type (acute myeloid leukemia \[AML\] or myelodysplastic syndromes \[MDS\] vs non-small cell lung cancer or mesothelioma). Patients receive vaccine comprising Wilms-tumor 1 (WT-1) analog peptide emulsified in Montanide ISA-51 subcutaneously (SC) once in weeks 0, 4, 6, 8, 10, and 12 and sargramostim (GM-CSF) SC twice in weeks 0, 4, 6, 8, 10, and 12 (on the day of and 2 days prior to each vaccination). Patients who have an immunologic response and have no disease progression may receive up to 6 more vaccinations approximately 1 month apart. Blood samples are collected at baseline, week 8, and week 14. Samples are examined by polymerase chain reaction (PCR) to measure levels of WT-1 and by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT to measure immune response. Bone marrow samples are collected from patients with AML or MDS at baseline and week 14. Samples are examined by PCR to measure levels of WT-1 and by multiparameter flow cytometry to measure residual disease.
Interventions
BIOLOGICALWT-1 analog peptide vaccine
BIOLOGICALincomplete Freund's adjuvant
BIOLOGICALsargramostim
GENETICpolymerase chain reaction
OTHERflow cytometry
OTHERimmunoenzyme technique
Sponsors
National Cancer Institute (NCI)
Innovive Pharmaceuticals
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Cytologically or histologically confirmed diagnosis of 1 of the following: * Acute myeloid leukemia, meeting the following criteria: * Documented Wilms tumor-1 (WT-1)-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease with real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) * Completed induction chemotherapy, achieved clinical remission, and completed postremission therapy OR achieved clinical remission and have no plans for further postremission chemotherapy (≥ 65 years of age) * Myelodysplastic syndromes, meeting the following criteria: * Documented WT-1-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease by RQ-PCR * International Prognostic Scoring System (IPSS) score of ≥ Int-2 * Not a candidate for cytotoxic chemotherapy * Non-small cell lung cancer, meeting the following criteria: * Positive tumor staining for WT-1 in \> 10% of cells * Stage III or IV disease * Completed chemotherapy, surgery, and/or radiotherapy * Mesothelioma, meeting the following criteria: * Positive tumor staining for WT-1 in \> 10% of cells * Unresectable or relapsed disease * Chemo-naive or received 1 prior chemotherapy regimen * Malignant pleural mesothelioma or peritoneal mesothelioma * No leptomeningeal disease * No CNS involvement PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Absolute neutrophil count ≥ 1,000/mm³ * Platelet count \> 50,000/mm³ (except for myelodysplastic syndromes where parameter is \> 20,000/mm³ and not transfusion dependent) * Bilirubin ≤ 2.0 mg/dL * AST and ALT ≤ 2.5 times upper limit of normal * Creatinine ≤ 2.0 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection requiring systemic antibiotics, antiviral, or antifungal treatments * No serious unstable medical illness PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 4 weeks since prior chemotherapy or radiotherapy * No concurrent systemic corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 2 years | Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0). |
| Immune Response | 2 years | Immune reactivity to the peptides will be measured in the same fashion for patients with hematologic or thoracic malignancies. Immune responses will be measured by T cell proliferative response and DTH against WT-1 peptides. In patients with adequate samples, T cell gamma interferon release as measured by ELISPOT will be performed as well. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vaccine Six vaccinations of the WT-1 peptide (1.0 ml of emulsion) will be administered on weeks 0, 4, 6, 8, 10 & 12. Vaccinations will be administered subcutaneously with sites rotated among extremities. Injection sites will be pre-stimulated with Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 & -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) if they have been appropriately instructed on SQ injection administration. Patients will keep a logbook noting the time & placement of the injection. Note: during each vaccination, the Sargramostim (GM-CSF) & the vaccine emulsion will be administered to the same anatomical site. This site will be marked by the patient or treating healthcare professional by a permanent marker pen. For patients who have a clinical, molecular, or immunologic response & have not had disease progression, they may receive up to 6 more vaccinations administered approximately every month.
WT-1 analog peptide vaccine | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
Immune Response
Immune reactivity to the peptides will be measured in the same fashion for patients with hematologic or thoracic malignancies. Immune responses will be measured by T cell proliferative response and DTH against WT-1 peptides. In patients with adequate samples, T cell gamma interferon release as measured by ELISPOT will be performed as well.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Immune Response | 10 participants |
Primary
Safety
Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0).
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Safety | 10 participants |