Vaccination With GM-K562 Cells in Patients With Advanced Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) After Allogeneic Hematopoetic Stem Cell Transplantation - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Collaborators:	Brigham and Women's Hospital National Institutes of Health (NIH)
Information provided by (Responsible Party):	Vincent T. Ho, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00809250

Purpose

The purpose of this research study is to determine if the GM-K562/leukemia cell vaccine can be safely given soon after allogeneic marrow or blood stem cell transplant. The GM-K562/leukemia cell vaccine is composed of a cultured cell line that has been genetically modified to secrete GM-CSF, a naturally occuring substance in the body that stimulates the immune system. The vaccine is a mixture of the GM-K562 cells (radiated to prevent them from growing in the participants body) with the participant's previously frozen and killed leukemia cells. By mixing the GM-K562 with the leukemia cells, we would like to study whether this vaccine combination will stimulate the participant's new immune system to recognize and fight against their MDS/AML cancer cells.

Condition	Intervention	Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome-Refractory Anemia With Excess Blasts	Biological: GM-K562/leukemia cell vaccine	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Vaccination With Lethally Irradiated Autologous Myeloblasts With Granulocyte Macrophage-colony Stimulating Factor Secreting K562 Cells (GM-K562) in Patients With Advanced MDS or AML After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Anemia Cancer Leukemia Myelodysplastic Syndromes

U.S. FDA Resources

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

Primary Outcome Measures:

To assess the safety of vaccination, as measured by vaccine related reactions and incidence of grade III-IV acute GVHD. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To assess the efficacy of vaccination with GM-K562/leukemia cell vaccine following allogeneic stem cell transplantation in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To characterize the biologic responses and leukemia specific immune responses after vaccination with GM-K562/leukemia cell vaccine following allogeneic stem cell transplant. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine duration of disease response, disease free and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	November 2008
Estimated Study Completion Date:	December 2026
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Cultured cell line genetically changed to secrete GM-CSF mixed with irradiated leukemia cells obtained from the participant. A total of 6 vaccine will be given. Vaccines 1-3 will be given once a week. Vaccines 4-6 will be given every other week.

Detailed Description:

Participants will be given the GM-K562/Leukemia call vaccine as in injection under the skin a total of six times. The first 3 vaccines will be given weekly and vaccines 4 through 6 will be given every other week. Therefore, it is expected that the vaccines will be completed over a period of 9 weeks.
During the 9 week vaccination period, participants will have physical exams to monitor for any side effects or graft-versus-host disease (GVHD). Bone marrow biopsies will be performed a the time of enrollment for this study, 4 weeks after completion of 6 GM-K562/Leukemia cell vaccines, and 1 year after the participants transplant.
As a way of testing whether the GM-K562/Leukemia cell vaccine is triggering any immune response to the participants leukemia, we will be injecting a small amount of leukemia cells (after they are killed with radiation) under the participants skin to see if the body will generate a reaction to the leukemia cells. This test is called a leukemia cell delayed hypersensitivity test (DTH). This test will be performed three times during the study, on the weeks of the 1st vaccine, 5th vaccine and 4 weeks after the 6th vaccine.
There are a total of 5 skin biopsies required as part of this study. Biopsies will be taken from the vaccination sites 2-3 days after the first and fifth vaccine. Similar biopsies will be taken from the DTH sites after the 1st vaccination, 5th vaccination and 4-6 weeks after the 6th vaccination.

Eligibility

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

Criteria

Inclusion Criteria:

Patients who have received an allogeneic bone marrow or peripheral blood stem cell transplant for AML, meeting one of the following: 1) AML arising from MDS or MDP 2)AML CR1 associated with high risk cytogenetics 3) AML transplanted in induction failure or relapse 4) AML transplanted in second remission or beyond 5) AML in patient 60 years or older
Patients who have received an allogeneic bone marrow or peripheral blood stem cell transplant for MDS-RAEB or CMML
18 years of age or older
Donor is a related or unrelated donor who is at least 9/10 matched at HLA-A, B, C, DRB1, and DQB1 by antigen level typing at class 1 and allele level typing at class II
Recipients of myeloablative or reduced intensity conditioning transplants are eligible
Patient must have sufficient autologous tumor cells banked at DFCI (on companion tissue banking protocol) for vaccine generation prior to transplantation
No active GVHD requiring systemic corticosteroid therapy
No conditions requiring systemic corticosteroid therapy greater than or equal to 20mg methylprednisolone or equivalent
No uncontrolled infection
Adequate hematopoietic engraftment with ANC >500 off growth factor support, and platelet >10k without transfusion
No non-hematologic toxicity of CTC Grade 3 or greater
ECOG Performance Status 0-2

Exclusion Criteria:

Recipients of cord blood transplant
Patients with uncontrolled CNS disease
Patients with relapsed/persistent disease after transplant who are expected to require rapid withdrawal of immune suppression, cytoreductive therapy, or have a life expectancy of < 3 months
Concurrent participation in other transplant clinical trials where GVHD and/or disease relapse are primary endpoints
Patients deemed medically or psychologically unfit by treating physician or study investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809250

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

Brigham and Women's Hospital

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Vincent Ho, MD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Vincent T. Ho, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00809250 History of Changes
Other Study ID Numbers:	08-160
Study First Received:	December 15, 2008
Last Updated:	January 23, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

vaccination
AML
CMML
MDS-RAEB

Additional relevant MeSH terms:

Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes

Preleukemia
Leukemia, Myelomonocytic, Acute
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on February 09, 2012