Clinical trial NCT01096602: Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission
Official title: Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
AML
Keywords: Dendritic Cell/AML vaccine
CT-011
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Medivation, Inc.
name: The Leukemia and Lymphoma Society
name: Dana-Farber Cancer Institute
First posted: 2010-03-31
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Immune Response
timeFrame: 2 years
measure: T-cell and Immune Response
timeFrame: 2 years
measure: Disease Response
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Jacalyn Rosenblatt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.