Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission

Acute Myelogenous Leukemia Clinical Trial

Official title:

Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01096602
• Other study ID #: 09-412
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: June 2024

Study information

• Verified date: June 2023
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute myelogenous leukemia (AML) arises from leukemia stem cells that are difficult to eradicate and serve as a reservoir for disease relapse following chemotherapy. A promising area of investigation is the development of immunotherapeutic approaches that stimulate the immune system to recognize leukemia stem cells as foreign and eliminate them. The purpose of this research study is to determine the safety of the Dendritic Cell AML Fusion Vaccine (DC AML vaccine) after participants have achieved a remission with chemotherapy. In this clinical trial, patients are treated with a tumor vaccine alone following standard of care chemotherapy. The DC AML vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells. It is hoped that DC AML vaccine will prevent or delay the disease from coming back.

Description:

- On this study participants will receive the DC AML vaccine and GM-CSF 4-8 weeks after completion of chemotherapy for acute myelogenous leukemia (AML). GM-CSF is a drug that stimulates white blood cells and is given with the DC AML Vaccine in an effort to enhance the effect of the vaccine. Participants will receive 2-3 doses of the vaccine at 4 week intervals. - All participants will undergo the following procedures: Isolation of tumor cells by either bone marrow biopsy or blood draw; Initial chemotherapy for AML with standard therapy; Leukopheresis (collection of white blood cells from the blood). - All participants will also have blood tests, a physical exam, and an electrocardiogram prior to each dose of vaccine. - Four weeks following the final vaccination, participants will undergo a skin test called "delayed-type hypersensitivity" (DTH). This is an injection of the tumor cells under the skin to measure how the immune system responds. The tumor cells are broken up and irradiated to prevent their growth.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 63
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Screening:

• Patients with AML at initial diagnosis or at first relapse
• 18 years of age or older
• ECOG Performance Status 0-2
• Life expectancy of greater than 9 weeks
• Laboratory values within limits outlined in the protocol
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Prior to Cell Collections for Dendritic Cell Generation:

• Patients must have obtained complete remission with chemotherapy defined by the absence of circulating blasts, and less then 5% blasts on bone marrow examination following hematopoietic recovery
• Resolution of all chemotherapy related Grade III-IV toxicity as per CTC criteria 4.0
• Laboratory values as outlined in the protocol
• For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or FISH will be followed post vaccination

Prior to Post-Chemotherapy Immunotherapy:

• Resolution of all chemotherapy related grade III-IV toxicity
• Laboratory values as outlined in the protocol
• At least 2 doses of fusion vaccine produced Exclusion Criteria:

Screening:

• Active or history of autoimmune disorders/conditions including Type 1 diabetes. Type II diabetes, vitiligo or stable hyperthyroidism will not be considered exclusion criteria
• HIV positive
• Significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
• Pregnant women
• Individuals with a history of a different malignancy are ineligible except for circumstances outlined in the protocol document

Prior to Cell Collection for Dendritic Cell Generation:

• Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
• Patients who choose to proceed with allogeneic or autologous transplant at the time of remission will not be vaccinated and will come off study

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• AML
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• DC AML Vaccine
Group 1: 2-3 doses of the vaccine at 4 week intervals

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Dana-Farber Cancer Institute, Medivation, Inc., National Institutes of Health (NIH), The Leukemia and Lymphoma Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity	To assess the toxicity associated with treating AML patients with DC/AML fusion cells in the post-chemotherapy setting	2 years
Secondary	Immune Response	To explore immunological response to DC/AML fusion vaccination in patients who have achieved a chemotherapy-induced remission.	2 years
Secondary	T-cell and Immune Response	To correlate levels of circulating activated and regulatory T cells with immunologic response	2 years
Secondary	Disease Response	To define anti-tumor effects by determining time to disease progression.	2 years