Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00398138
• Collaborator: National Cancer Institute (NCI) (NIH), Innovive Pharmaceuticals (Industry)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 32
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lung Cancer; Malignant Mesothelioma; Myelodysplastic Syndromes; Primary Peritoneal Cavity Cancer	Biological: WT-1 analog peptide vaccine; Biological: incomplete Freund's adjuvant; Biological: sargramostim; Genetic: polymerase chain reaction; Other: flow cytometry; Other: immunoenzyme technique	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Biological: WT-1 analog peptide vaccine; Biological: incomplete Freund's adjuvant; Biological: sargramostim; Genetic: polymerase chain reaction; Other: flow cytometry; Other: immunoenzyme technique

Outcome Measures

Primary Outcome Measures

1. Safety [2 years]

   Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0).

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• Innovive Pharmaceuticals

Investigators

• Principal Investigator: Lee M. Krug, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00398138
• Other Study ID Numbers: 06-085; P30CA008748; P01CA023766; MSKCC-06085
• First Posted: Nov 10, 2006
• Last Update Posted: Mar 2, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: 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
• Additional relevant MeSH terms: Leukemia; Lung Neoplasms; Preleukemia; Mesothelioma; Mesothelioma, Malignant; Myelodysplastic Syndromes; Syndrome; Sargramostim; Freund's Adjuvant

Study Results

Participant Flow

Arm/Group Title	Vaccine
Arm/Group Description	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
Period Title: Overall Study
STARTED	12
COMPLETED	10
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Vaccine
Arm/Group Description	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
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 50%
>=65 years	5 50%
Sex: Female, Male (Count of Participants)
Female	2 20%
Male	8 80%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Safety
Description	Toxicities will be tabulated according to the NCI Common Toxicity (version 3.0).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vaccine
Arm/Group Description	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
Measure Participants	10
Number [participants]	10 100%

2. Primary Outcome

Title	Immune Response
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vaccine
Arm/Group Description	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
Measure Participants	10
Number [participants]	10 100%

Adverse Events

Arm/Group Title	Vaccine
Arm/Group Description	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
All Cause Mortality
	Vaccine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vaccine
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Nervous system disorders
Syncope	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/10 (20%)	2
Vascular disorders
Edema: head and neck	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Vaccine
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Lymphopenia	1/10 (10%)
Platelets	4/10 (40%)
General disorders
Fatigue (asthenia, lethargy, malaise)	4/10 (40%)
Infections and infestations
Leukocytes (total WBC)	4/10 (40%)
Neutrophils/granulocytes (ANC/AGC)	2/10 (20%)
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	6/10 (60%)
Glucose, high (hyperglycemia)	10/10 (100%)
Hemoglobin	6/10 (60%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.