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

Primary Purpose

Leukemia, Lung Cancer, Malignant Mesothelioma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

WT-1 analog peptide vaccine

incomplete Freund's adjuvant

sargramostim

polymerase chain reaction

flow cytometry

immunoenzyme technique

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

vaccine

Arm 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.

Outcomes

Primary Outcome Measures

Safety

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

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00398138

First Posted

November 9, 2006

Last Updated

February 2, 2016

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI), Innovive Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00398138

Brief Title

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

Official Title

Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

October 2006 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI), Innovive Pharmaceuticals

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Lung Cancer, Malignant Mesothelioma, Myelodysplastic Syndromes, Primary Peritoneal Cavity Cancer

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

vaccine

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

WT-1 analog peptide vaccine

Intervention Type

Biological

Intervention Name(s)

incomplete Freund's adjuvant

Intervention Type

Biological

Intervention Name(s)

sargramostim

Intervention Type

Genetic

Intervention Name(s)

polymerase chain reaction

Intervention Type

Other

Intervention Name(s)

flow cytometry

Intervention Type

Other

Intervention Name(s)

immunoenzyme technique

Primary Outcome Measure Information:

Title

Safety

Description

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

Time Frame

2 years

Title

Immune Response

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lee M. Krug, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20400682

Citation

Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva V, Zhang R, Wolchok JD, Yuan J, Pinilla-Ibarz J, Berman E, Weiss M, Jurcic J, Frattini MG, Scheinberg DA. Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood. 2010 Jul 15;116(2):171-9. doi: 10.1182/blood-2009-10-250993. Epub 2010 Apr 16.

Results Reference

result

Links:

URL

http://www.mskcc.org/

Description

Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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