Clofarabine, Gemcitabine, and Busulfan Followed by Donor Stem Cell Transplantation in Treating Participants With Chronic Lymphocytic Leukemia (CLL)

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of gemcitabine when administered with
busulfan and clofarbine.

II. To estimate the day 100 treatment-related mortality (TRM) for the preparative regimen
busulfan, clofarabine, and gemcitabine followed by allogeneic hematopoietic cell
transplantation (HCT) for patients with chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

I. To determine the rate of progression-free survival (PFS), graft versus host disease
(GVHD), engraftment, and overall survival (OS) for this treatment regimen at one year post
treatment completion.

OUTLINE: This is a dose-escalation study of gemcitabine.

Participants receive gemcitabine intravenously (IV) over 10-25 minutes on days -6 and -4,
clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with
matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to
-1. Starting day -2, participants receive tacrolimus orally (PO) daily for up to 6 months.
Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive
methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim subcutaneously (SC)
once daily (QD) beginning 1 week after transplant until blood cell levels return to normal.

After completion of study treatment, participants are followed up at 3, 6 and 12 months, then
every 6 months for 1 year.

Inclusion Criteria:

- Patients with chronic lymphocytic leukemia, prolymphocytic leukemia, or Richter's
transformation who are eligible for allogeneic transplantation and are not eligible
for protocols of higher priority

- A 10/10 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or
unrelated donor

- Left ventricular ejection fraction (EF) > 40%

- Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and corrected
diffusion capacity of the lung for carbon monoxide (DLCO) > 40%

- Serum creatinine < 1.6 mg/dL

- Serum bilirubin < 2 X upper limit of normal

- serum glutamate pyruvate transaminase (SGPT) < 2X upper limit of normal

- Voluntary signed, written Institutional Review Board (IRB)-approved informed consent

- Men and women of reproductive potential must agree to follow accepted birth control
methods for the duration of the study. Female subject is either post-menopausal or
surgically sterilized or willing to use an acceptable method of birth control (i.e., a
hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with
spermicide, or abstinence) for the duration of the study. Male subject agrees to use
an acceptable method for contraception for the duration of the study

Exclusion Criteria:

- Patient with active central nervous system (CNS) disease

- Pregnant (positive beta human chorionic gonadotropin [HCG] test in a woman with child
bearing potential defined as not post-menopausal for 12 months or no previous surgical
sterilization) or currently breast-feeding. Pregnancy testing is not required for
post-menopausal or surgically sterilized women

- Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus
(HTLV)-I, hepatitis B, or hepatitis C

- Active uncontrolled bacterial, viral or fungal infections

- Patient has received other investigational drugs within 1 week before enrollment