Reduced Intensity Stem Cell Transplantation for Chronic Lymphocytic Leukemia Followed by Vaccination - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Brigham and Women's Hospital
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00442130

Purpose

The purpose of this research study is to assess the safety and immune activity of a vaccine made from the participant's own cancer cells, when administered after a reduced intensity transplant. In recent years, researchers at Dana-Farber Cancer Institute have discovered that vaccines made from a patients's own cancer cells, 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	Phase
Chronic Lymphocytic Leukemia	Biological: GM-K562 vaccine Procedure: stem cell transplantation	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Tacrolimus Sargramostim Granulocyte-macrophage colony-stimulating factor Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety Study
Official Title:	Reduced Intensity Stem Cell Transplantation for Advanced Chronic Lymphocytic Leukemia Followed by Vaccination With Lethally Irradiated Autologous Tumor Cells Admixed With Granulocyte Macrophage-Colony Stimulating Factor Secreting K562 Cells

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

Primary Outcome Measures:

To assess the safety and toxicity of vaccination with lethally irradiated autologous CLL cells admixed with GM-562 cells following reduced intensity allogeneic stem cell transplant for CLL patients with advanced disease. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To characterize the biologic activity in response to vaccination with lethally irradiated autologous CLL cells admixed with GM-562 cells, following reduced intensity allogeneic stem cell transplant [ Time Frame: 2 years ] [ Designated as safety issue: No ]
to estimate duration of disease response, disease free and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	February 2007
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Intervention Details:

The vaccine will be administered over 2 cycles of 7 weeks each: Cycle 1 vaccine will begin 1 month after stem cell transplant. Cycle 2 vaccine will be given approximately one month after discontinuing tacrolimus. The vaccine will be given 6 times over 2 months. Once a week for three weeks then every other week for 3 vaccines.

Participants will be admitted to the hospital for approximately 8 days to receive chemotherapy and stem cell transplantation

Detailed Description:

This study can be divided into four phases: 1) Screening; 2) Reduced intensity transplant phase; 3) Vaccinations (cycle 1 and cycle 2:each cycle lasts 7 weeks) and 4) Vaccine completion.
Screening Phase: After signing the consent form, participants will be asked to undergo some screening tests and procedures to find out if they are eligible to participate in the study. These tests and procedures are likely to be part of regular cancer care and may be done even if the patient does not take part in the research study. It is important to note that if insufficient numbers of the participants leukemia cells to generate vaccine were collected on the CLL collection and banking study (DFHCC study #06-200), then they will not be eligible to participate in this study.
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 chemotherapy and stem cell transplant. The minimum duration of hospitalization for the procedure is approximately 8 days. Undergoing transplant involves the following procedures and treatments: Central intravenous catheter; chemotherapy; medications to prevent graft versus host disease (GVHD); medication to prevent infections; physical exams; blood tests and bone marrow biopsy and aspirate.
Vaccination Phase: Vaccinations will be given in two cycles, of seven weeks each, that are identical with the exception of when they are administered. Cycle 1 vaccination will begin approximately one month after the stem cells have been infused, provided there is no significant evidence of GVHD. Cycle 2 vaccination will be being approximately one month after discontinuing tacrolimus, provided there is no evidence of severe acute or chronic GVHD. The vaccine will be given 6 times over a period of two months. The participant will receive vaccination shots once weekly for 3 vaccines and then every other week for 3 vaccines.
Skin biopsies will be done before the first and after the fifth vaccinations. Current status of the participants CLL will be assessed to determine how the disease has responded to transplant and vaccination. These tests include analysis of bone marrow and blood tests.
Vaccine completion phase: After one cycle of vaccination is completed, the participant will return to the outpatient clinic monthly for check-ups for 6 visits, to monitor the effects of the vaccine.
Since this trial involves the use of genetically modified cells, it is recommended that participants on this trial undergo annual checkups for at least 20 years, in order to monitor for long term effects of the vaccination treatment.

Eligibility

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

Criteria

Inclusion Criteria:

Advanced CLL, defined as no response or progressive disease during standard fludarabine based regimen; or, evidence of progressive disease within 24 months of completion of fludarabine regimen; or, intolerance to fludarabine; or, failure to achieve complete remission following salvage regimen.
< 30% involvement of the bone marrow by CLL and no sites of adenopathy > 3cm
(8/8) HLA matched related or unrelated donor available.
Must have prior banked tumor, collected by peripheral blood draw, leukapheresis, bone marrow biopsy or by lymph node dissection, per DF/HCC protocol 06-200
ECOG performance status 0-2

Exclusion Criteria:

Serum creatinine greater than or equal to 2.0mg/dl
ALT or AST greater than or equal to 3x ULN
Total bilirubin greater than or equal to 2.0mg/dl (except for patients with Gilbert's syndrome)
Cardiac ejection fraction <30%
HIV infection
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00442130

Contacts

Contact: Catherine J. Wu, MD	617-632-5943	cwu@partners.org
Contact: Laura Spring		lspring@partners.org

Locations

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

Sponsors and Collaborators

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Investigators

Principal Investigator:

Catherine J. Wu, MD

Dana-Farber Cancer Institute

More Information

Responsible Party:	Dana-Farber Cancer Institute ( Catherine Wu, MD )
Study ID Numbers:	06-196
Study First Received:	February 27, 2007
Last Updated:	December 20, 2007
ClinicalTrials.gov Identifier:	NCT00442130
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

GM-CSF
GM-K562
vaccine

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Tacrolimus
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009