Blockage of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation - Full Text View

Sponsor:	Beth Israel Deaconess Medical Center
Collaborators:	Dana-Farber Cancer Institute Brigham and Women's Hospital Rambam Health Care Campus Gateway for Cancer Research Department of Defense
Information provided by (Responsible Party):	David Avigan, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT01067287

Purpose

The purpose of this research study is to determine the safety of CT-011 alone, as well as the combination of the Dendritic cell fusion vaccine and CT-011, after autologous stem cell transplantation (ASCT). We are also trying to find out what effect the combination has on the disease, including if it is more successful in preventing or delaying the disease from coming back, compared to treatment with autologous transplantation alone. ASCT is a standard therapy for multiple myeloma that is often successful in significantly decreasing the amount of cancer in the body. CT-011 is an investigational monoclonal antibody. Monoclonal antibodies are a type of drug given by infusion into a vein and are known to target specific cells (in this case, cells in the immune system). The dendritic cell fusion vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells. Unlike a standard vaccine that is used to prevent infections, cancer vaccines are being studied to see if they can fight cancers that are already in the body.

Condition	Intervention	Phase
Multiple Myeloma	Drug: CT-011 Biological: Dendritic Cell Fusion Vaccine	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:	Blockage of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

U.S. FDA Resources

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

Primary Outcome Measures:

First Stage: To explore immunological response to CT-011 in the post transplant period. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Second Stage: To determine if cellular immunity is induced by treatment with monoclonal antibody CT-011 and DC/myeloma fusion cells in conjunction with stem cell transplant. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

First Stage: To assess the toxicity associated with treating multiple myeloma patients with CT-011 in the post- autologous transplant setting. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Second Stage: To assess the toxicity associated with treating multiple myeloma patients with the combination with DC/myeloma fusion vaccine following autologous transplant. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Second Stage: To correlate levels of circulating activated and regulatory T cells with immunologic response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Second Stage: To define anti-tumor effects using serum markers, radiological studies, and time to progression. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	35
Study Start Date:	March 2010
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group 1 Monoclonal antibody CT-011 will be given 1-3 months following autologous transplant. 3 doses will be given at 6 week intervals.	Drug: CT-011 Infusions starting one to three months following autologous transplant at 6 week intervals for a total of 3 doses
Active Comparator: Group 2 Vaccination with DC/myeloma fusion cells will be given 1-3 months following autologous transplant. Vaccination will be given at 6 weeks intervals. The monoclonal antibody CT-011 will be given 1 week following each vaccination. 3 doses of CT-011 will be given at 6 week intervals.	Drug: CT-011 Infusions starting one to three months following autologous transplant at 6 week intervals for a total of 3 doses Biological: Dendritic Cell Fusion Vaccine One week following each infusion of CT-011

Detailed Description:

There are two groups in this study: Group 1: All participants in this study group will receive infusions of CT-011 starting one to three months following autologous transplant. Participants in this group will receive a total of 3 doses of CT-011 at 6 week intervals. Group 2: All participants in this group will receive infusions of CT-011 starting one to three months following autologous transplant. 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 Dendritic Cell Fusion Vaccine one week following each infusion of CT-011.
All participants (Group 1 and Group 2) will receive the following procedures: 1) Initial therapy for multiple myeloma: All participants will receive standard therapy to reduce the number of multiple myeloma cells in the body. 2) Prior to stem cell mobilization participants will undergo a physical exam, medical history, and blood tests to measure blood counts, liver and kidney function, multiple myeloma protein level, and research testing to measure the immune response against the multiple myeloma cells. A small amount of bone marrow will be removed from the participants hip. Participants will also undergo a skin test called "delayed-type hypersensitivity (DTH). 3) Prior to the autologous stem cell transplant, we will harvest stem cells from the participants blood and store then for the future transplant through a process called leukapheresis. 4) Within a few weeks of successful stem cell collection, participants will be admitted to the hospital for high dose chemotherapy with autologous stem cell transplantation (ASCT). 5) Approximately 1-3 months following ASCT, participants will undergo additional tests to assess their eligibility to proceed with treatment with CT-011 alone (group 1) or the combination of CT-011 and vaccination (group 2).
If the post-transplant eligibility results meet the study requirements participants will receive 3 infusions of CT-011 at 6 week intervals. Prior to each infusion of CT-011, participants will undergo the following procedures: blood tests, urine sample, physical exam and EKG. Participants will be seen weekly to review any side effects, what medications they are taking, and will have a blood test an physical exam.
For Group 2 participants only: Prior to autologous transplant, Group 2 participants will undergo several procedures to make the Dendritic Cell Fusion Vaccine. 1) Dendritic Cell Collection via leukapheresis 2) Tumor cell collection from the participants bone marrow. One week after receiving the CT-011 infusion, Group 2 participants will receive the study vaccine for a total of 3 vaccines.
After the final treatment both Group 1 and Group 2 participants will receive a tumor DTH injection and DTH to Candida into the skin. At one, three and six months following the last study treatment participants will have blood tests, urine test, bone marrow aspirate/biopsy and a skeletal survey. At two, four and five months, participants will have a blood test.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with multiple myeloma who are potential candidates for high doses chemotherapy with stem cell rescue
Patients must not have active of history of autoimmune disorders/conditions including Type I diabetes, Type II diabetes, vitiligo or stable hypothyroidism will not be considered exclusion criteria
Patients with measurable disease as defined by a history of an elevated M component in plasma, urine, or free kappa/lambda light chains in the serum
18 years of age or older
ECOG Performance Status of 0-1 with a greater than nine week life expectancy
>20% bone marrow involvement in plasmacytoma amenable to resection under local anesthesia
Negative pregnancy test and adequate contraception method(s)
DLCO (adjusted) > 50%
Cardiac Ejection Fraction > 45%
Laboratory results as defined in protocol

Exclusion Criteria:

History of clinically significant venous thromboembolism
Clinically significant autoimmune disease
HIV positive
Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
Pregnant or lactating women
History of allogeneic bone marrow/stem cell transplant

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01067287

Contacts

Contact: David Avigan, MD

617-667-9920

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: David Avigan, MD
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Nikhil Munshi, MD
Israel
Rambam Medical Center	Recruiting
Haifa, Israel
Contact: Irit Avivi, MD
Principal Investigator: Irit Avivi, MD

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Rambam Health Care Campus

Gateway for Cancer Research

Department of Defense

Investigators

Principal Investigator:

David Avigan, MD

Beth Israel Deaconess Medical Center

More Information

No publications provided

Responsible Party:	David Avigan, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT01067287 History of Changes
Other Study ID Numbers:	09-061
Study First Received:	July 29, 2009
Last Updated:	May 22, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

dendritic cell fusion vaccine
CT-011
autologous stem cell transplant

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 24, 2012