Reduced Intensity Stem Cell Transplantation for Chronic Lymphocytic Leukemia Followed by Vaccination
Reduced Intensity Stem Cell Transplantation for Chronic Lymphocytic Leukemia Followed by Vaccination
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.
-  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 participant's leukemia cells to
 generate vaccine were collected on the CLL collection and banking study (DF/HCC 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 after 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.
Inclusion Criteria:

 -  Advanced CLL, defined as no response or progressive disease during standard nucleoside
 analogue based regimen; or, evidence of progressive disease within 24 months of
 completion of nucleoside analogue regimen; or, intolerance to fludarabine; or, failure
 to achieve complete remission following salvage regimen.

 -  no sites of adenopathy > 5cm

 -  (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 greater than or equal to 30%

 -  HIV infection

 -  Pregnancy