Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in MPM Patients After MSK10-134

Malignant Pleural Mesothelioma Clinical Trial

Official title:

Randomized Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy (MSK10-134)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01890980
• Other study ID #: 2011-0289
• Secondary ID: HRPO Log Number
• Status: Completed
• Phase: Phase 2
• Start date: April 2013
• Est. completion date: September 11, 2018

Study information

• Verified date: July 2020
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical research study is to learn if the Wilms Tumor-1 (WT1) vaccine, when given in combination with montanide and GM-CSF, can help to prevent or delay mesothelioma from coming back after surgery and treatment. The safety of this vaccine will also be tested.

Montanide and GM-CSF are designed to cause white blood cells to grow, which may help to increase the immune response.

WT1 is a protein in cancer cells that regulates gene expression and causes cell growth. Mesothelioma tumors usually have high levels of WT1. The WT1 vaccine is designed to cause the increased immune response created by other drug combinations (like montanide and GM-CSF) to be directed at mesothelioma.

Description:

Study Drug Administration:

When this study opened, it had 2 groups. In 1 of the groups, participants only received montanide and GM-CSF. This group has stopped enrolling participants. All participants will now receive montanide, GM-CSF, and the WT1 vaccine.

You will receive montanide through an injection under the skin every 2 weeks for up to 12 weeks (6 doses). You will receive the WT-1 vaccine at the same time that you receive montanide.

You will also receive GM-CSF through an injection under the skin on the day you receive montanide and 2 days before you receive montanide each time (12 doses of GM-CSF total). If the doctor thinks it is in your best interest, you might be taught how to inject the GM-CSF yourself.

Study Visits:

On Week 2, Week 6, and Week 12, you will have a physical exam, including measurement of your weight and vital signs. You will also be asked about any drugs you may be taking and any side effects you may be having.

At Weeks 6 and 12, the following tests and procedures will also be performed:

• Your performance status will be recorded.

• Blood (about 4 teaspoons) will be drawn for routine tests.

• Blood (about 2 tablespoons) will be drawn to check your level of SMRP.

• Blood (about 7 tablespoons) will be drawn to check your immune response to the study drug(s) (Week 12 only).

At Week 12 or earlier if the doctor thinks it is needed, you will have a chest x-ray and CT scan of the chest to check the status of the disease.

Length of Study:

You will receive the study drugs for up to 12 weeks. You will be taken off study if the study doctor thinks it is in your best interest or you have intolerable side effects.

Your participation in the study will be over after the follow-up visits.

Follow-Up:

Within 30 days after you stop receiving the study drugs, you will have a physical exam, including measurement of your weight and vital signs. You will also be asked about any drugs you may be taking and any side effects you may be having.

Every 3 months for up to 2 years after you stop receiving the study drugs, the following tests and procedures will be performed:

• Your medical history will be recorded

• You will have a physical exam, including measurement of your weight and vital signs.

• You will be asked about any drugs you may be taking and any side effects you may be having.

• Blood (about 2 tablespoons) will be drawn for routine tests and to measure your levels of SMRP.

• You will have a CT scan of the chest to check the status of the disease

This is an investigational study. GM-CSF is FDA approved for helping the immune system in patients with acute myelogenous leukemia. Montanide and Wilms Tumor-1 (WT1) are not FDA approved or commercially available. They are currently being used for research purposes only.

The combination of WT-1 vaccine with montanide and GM-CSF is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 60 patients will take part in this multicenter study. Up to 20 will be enrolled at MD Anderson.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 11, 2018
• Est. primary completion date: September 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Pathologic diagnosis of malignant pleural mesothelioma (MPM) confirmed at participating institution.

2. Positive immunohistochemical staining for WT-1 (greater than 10% of cells).

3. Completion of multimodality therapy. This must include surgical resection by either pleurectomy/decortication or extrapleural pneumonectomy. The surgery should be performed with the intent of complete resection, though patients with an R1 resection will still be eligible. Patients should have also received treatment with chemotherapy and/or radiation. Patients with an R2 resection are also eligible as long as the sites of residual disease is treated post-operatively with radiotherapy.

4. 4-12 weeks since completion of combined modality therapy.

5. Age >/= 18 years.

6. Karnofsky performance status >/= 70%

7. Hematologic parameters: Absolute neutrophil count >/= 1000/mcL, Platelets > 50 K/mcL.

8. Biochemical parameters: Total bilirubin </= 2.0 mg/dl, AST and ALT </= 2.5 x upper limits of normal, Creatinine </= 2.0 mg/dl.

9. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as a female that is able to have children that has not been surgically sterilized or amenorrheic for 12 consecutive months. The patient, if a man, agrees to use effective contraception or abstinence.

Exclusion Criteria:

1. The patient is pregnant (confirmed by urine or serum Beta-HCG if applicable) or is breastfeeding.

2. Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments

3. Patients with a serious unstable medical illness that would prevent compliance with the protocol or another active cancer.

4. Patients taking systemic corticosteroids.

5. Patients with a known pre-existing immunodeficiency syndrome.

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Biological:
• WT-1-vaccine Montanide + GM-CSF
Treatment of 6 injections over 12 weeks, administered on weeks 0, 2, 4, 6, 8, and 10. All receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination and may be self administered with appropriate instruction. Participants keep a logbook noting the time and placement of the injection, and will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide which will be administered by a nurse (not self-administered) subcutaneously to the same anatomical site as the GM-CSF as marked by the patient or treating healthcare professional by a permanent marker pen.
• Montanide adjuvant + GM-CSF
Treatment of 6 injections over 12 weeks, administered on weeks 0, 2, 4, 6, 8, and 10. All receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination and may be self administered with appropriate instruction. Participants keep a logbook noting the time and placement of the injection, and will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide which will be administered by a nurse (not self-administered) subcutaneously to the same anatomical site as the GM-CSF as marked by the patient or treating healthcare professional by a permanent marker pen.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Memorial Sloan Kettering Cancer Center, Sellas Life Sciences Group, U.S. Army Medical Research and Development Command

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-Year Progression Free Survival	Number of participants with 1-year progression free survival following treatment with WT-1 analog peptide vaccine + GM-CSF or Montanide + GM-CSF after completion of combined modality therapy for Malignant Pleural Mesothelioma (MPM) Progression free survival calculated from date of randomization to date of progression, death or last follow-up.	1 Year

External Links

•   University of Texas MD Anderson Cancer Center Website