GM-CSF Vaccinations After Allogeneic Blood Stem Cell Transplantation in Patients With Advanced Myeloid Malignancies - Full Text View

Purpose

The purpose of this study is to investigate whether the addition of a vaccine after participants reduced intensity transplant will be safe and beneficial. The vaccine used in this trial, called GVAX, will be made from the participants own leukemia cells, and will be given between 1-4 months after transplant. In recent years, researchers have discovered that GVAX vaccine made from the patient's own cancer calls that have been engineered in the laboratory to produce a protein called GM-CSF, can be effective in stimulating a powerful immune response specific to that cancer.

Condition	Intervention
Myelodysplastic Syndrome RAEB-I or RAEB-II Refractory Acute Myeloid Leukemia Refractory CML Myeloid Blast Crisis	Biological: GM-CSF secreting leukemia vaccine

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	GM-CSF Secreting Leukemia Cell Vaccinations After Allogeneic Non-myeloablative Peripheral Blood Stem Cell Transplantation in Patients With Advanced Myelodysplastic Syndrome or Refractory Acute or Advanced Chronic Myeloid Leukemia

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 Myelodysplastic Syndromes

Drug Information available for: Sargramostim

U.S. FDA Resources

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

Primary Outcome Measures:

Feasibility as measured by ability to generate sufficient vaccine, and ability for this patient population to initiate vaccination between day 30 to day 45 after transplant. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety of GVAX vaccination as measured by grade III-IV acute GVHD, and CTC grade 3 or higher non-hematologic toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
biologic activity of GVAX vaccination [ Time Frame: 3 years ] [ Designated as safety issue: No ]
disease free and overall survival. [ Time Frame: TBD ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	June 2004
Study Completion Date:	September 2009
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Vaccine given subcutaneously or intradermally on the leg, arm, or abdomen 6 times. The first three vaccines will be given once a week for three weeks. The last three vaccines will be given once every other week for three doses.

Detailed Description:

This trial can be divided into three phases: 1) Pre-transplant phase; 2) Reduced intensity transplant phase; 3) Vaccination phase.
Pre-transplant phase: Once a suitable donor has been identified, the participant will undergo a battery of standard pre-transplant tests and procedure to collect their leukemia cells for vaccine generation. Blood tests, heart function test, pulmonary function test, tuberculosis test, bone marrow aspirate and biopsy, and leukemia cell collection through leukapheresis.
Allogeneic reduced intensity stem cell transplant phase: The transplant phase of the study will begin when the participant is admitted to the hospital to receive the chemotherapy and stem cell transplant. The minimum duration of hospitalization for the procedure is approximately 8 days. In the week before the participant receives the stem cells, they will be treated with chemotherapy through a central line. The goal of chemotherapy is to both control the cancer and suppress the immune system so that the body will not reject the donor stem cells.
Just prior to and immediately following the infusion of stem cells, participants will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the body. After the transplant, participants will also take antibiotic medication to help prevent possible infections.
Sargramostim (GM-CSF, leukine), a white blood cell growth factor, will be given daily subcutaneously starting the day after the stem cell transplant until blood counts have recovered.
After the stem cell infusion, participants will be examined and have blood tests weekly for 1 month. Between 30-45 days after the transplant, a bone marrow biopsy will be performed to assess the status of the disease and to look for evidence of the donor's cells in the bone marrow.
Vaccination Phase: After the bone marrow biopsy 30-45 days after the transplant, the participant will begin to receive the vaccinations. The vaccine will be administered subcutaneously and intradermally on the arm, leg, or abdomen 6 times over a period of 9 weeks. The first 3 vaccinations will occur once a week for 3 consecutive weeks, and the last 3 vaccines will be given once every other week over 6 weeks. All vaccinations may be given as an outpatient in the clinic. During this period of time, participants will be closely monitored on a weekly basis to monitor for side effects. Before the first and after the fifth and sixth vaccinations, a small amount of the participants leukemia cells will be injected under the skin to see if the immune system will react against it and cause redness and swelling.
About 4 weeks after the last vaccination (6th), a bone marrow aspirate and biopsy will be performed to assess the status of the disease.
After the 1st and 5th vaccinations, a skin biopsy will be performed to assess for response at the vaccine site. These biopsies are relatively simple outpatient procedures.

Eligibility

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

Criteria

Inclusion Criteria:

AML, MDS-RAEB or RAEB-T, CML, myeloid blast crisis not in remission or CML accelerated phase. Subjects must have > 5% blasts in bone marrow or peripheral blood prior to admission for transplant.
HLA 6/6 matched related or unrelated donor available
ECOG Performance Statue 0-2
18 years of age or older

Exclusion Criteria:

Uncontrolled infection
Leukemia with active CNS involvement
Serum creatinine greater than 2.0 mg/dl
ALT or AST greater than 3 x ULN
Total bilirubin greater than 2.0 mg/dl
Positive HIV or HTLV-1 serology
Prior allogeneic stem cell transplant

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426205

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

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:	NCT00426205 History of Changes
Other Study ID Numbers:	04-023
Study First Received:	January 23, 2007
Last Updated:	March 15, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

GM-CSF
GVAX
Cancer vaccine
blood stem cell transplantation

MDS
AML
CML

Additional relevant MeSH terms:

Anemia, Refractory, with Excess of Blasts
Blast Crisis
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Anemia, Refractory
Anemia
Hematologic Diseases

Bone Marrow Diseases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on May 22, 2013