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

Purpose

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) alone, as well as of the combination of CT-011, after participants have achieved a remission with chemotherapy. In this clinical trial, patients are treated with a tumor vaccine alone or in combination with CT-O11, an investigational monoclonal antibody that may augment response to vaccination. Monoclonal antibodies are known to target specific cells (in this case, cells in the immune system). This immunotherapy may help to control leukemic cells that are resistant to chemotherapy and prevent disease recurrence. 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 the combination of DC AML vaccine and CT-011 will prevent or delay the disease from coming back.

Condition	Intervention	Phase
Acute Myelogenous Leukemia AML	Biological: DC AML Vaccine Drug: CT-011	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
First Stage: To assess the toxicity associated with treating AML patients with DC AML fusion cells in the post-chemotherapy setting
Toxicity [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Second Stage: To assess the toxicity associated with treating AML patients with a combination of DC AML fusion cells and CT-011 following a chemotherapy induced remission

Secondary Outcome Measures:

Immune response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
First Stage: To explore immunological response to DC AML Fusion vaccination in this patient population.
Tumor regression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Second stage: To determine if cellular immunity is induced by treatment with monoclonal antibody CT-011 and DC/AML fusion cells in patients who have obtained a complete remission following induction chemotherapy.
Time to disease progression [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
Second Stage: To define anti-tumor effects by determining time to disease progression.

Estimated Enrollment:	35
Study Start Date:	May 2010
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 DC AML Fusion Vaccine	Biological: DC AML Vaccine Group 1: 3 doses of the vaccine at 4 week intervals Group 2: Given two weeks following CT-011 infusion
Experimental: Group 2 CT-011 and DC AML Vaccine	Biological: DC AML Vaccine Group 1: 3 doses of the vaccine at 4 week intervals Group 2: Given two weeks following CT-011 infusion Drug: CT-011 Infusion given at 6 week intervals for a total of 3 doses

Detailed Description:

This study is divided into two groups: Group 1 participants will receive the DC AML Fusion Vaccine and Group 2 participants will receive the CT-011 and the DC AML vaccine. The first 10 participants will be in Group 1 and the remaining 25 will be in Group 2.
Group 1 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 in this group will receive 3 doses of the vaccine at 4 week intervals.
Group 2 participants will receive infusions of CT-011 4-8 weeks after completion of chemotherapy for AML. Participants in this group will receive a total of 3 doses of CT-011 at 6 week intervals. In addition, they will receive a vaccination of the DC AML vaccine two weeks following each infusion of CT-011.
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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01096602

Contacts

Contact: Jacalyn Rosenblatt, MD	617-667-9920	jrosenb1@bidmc.harvard.edu
Contact: Emma Breault	617-667-5984	ebreault@bidmc.harvard.edu

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

National Institutes of Health (NIH)

CureTech Ltd

Investigators

Principal Investigator:

Jacalyn Rosenblatt, MD

Beth Israel Deaconess Medical Center

More Information

No publications provided

Responsible Party:	Jacalyn Rosenblatt, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT01096602 History of Changes
Other Study ID Numbers:	09-412
Study First Received:	March 29, 2010
Last Updated:	May 13, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

Dendritic Cell/AML vaccine
CT-011

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on May 21, 2013