Fludarabine, Bendamustine, and Rituximab in Treating Participants With Lymphoid Cancers Undergoing Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine engraftment and dose limiting toxicity (DLT) of bendamustine in patients with
lymphoid malignancies undergoing non-myeloablative allogeneic hematopoietic transplantation.

SECONDARY OBJECTIVES:

I. To monitor the risk of graft-versus-host disease (GVHD) and clinical responses.

OUTLINE: This is a dose escalation study of bendamustine.

Participants receive rituximab intravenously (IV) over 5-7 hours on days -13 and -6,
fludarabine IV over 1 hour and bendamustine IV over 1 hour on days -5 to -3, and tacrolimus
IV starting on day -2 and orally (PO) after hospital discharge for 6 to 8 months.
Participants with matched unrelated donor (MUD) receive thymoglobulin on days -2 and -1.
Participants undergo allogenic stem cell transplant over 30-45 minutes on day 0. Participants
receive rituximab IV over 5-7 hours on days 1 and 8 and methotrexate IV over 30 minutes on
days 1, 3, and 6. Participants with MUD also receive methotrexate IV on day 11. Participants
receive filgrastim (G-CSF) subcutaneously (SC) once daily starting on day 7 until white blood
cell counts recover.

After completion of study treatment, participants are followed up every 3 months during year
1 and every 6 months for up to 3 years.

Inclusion Criteria:

- Patients with CD20 + chronic lymphocytic leukemia (CLL), marginal zone, mantle cell
and follicular lymphoma or T-cell lymphoid malignancies who are eligible for
allogeneic transplantation.

- Patients with relapsed diffuse large B-cell lymphoma may be included if they were not
eligible for autologous transplantation.

- A fully-matched sibling donor or matched unrelated donor.

- Left ventricular ejection fraction (EF) > 40% with no uncontrolled arrhythmias or
symptomatic heart disease.

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

- Serum creatinine < 1.6 mg/dL.

- Serum bilirubin < 3 X upper limit of normal.

- Serum glutamate pyruvate transaminase (SGPT) < 3 X upper limit of normal.

- Voluntary signed, written Institutional Review Board (IRB)-approved informed consent
before performance of any study-related procedure not part of normal medical care,
with the understanding that consent may be withdrawn by the subject at any time
without prejudice to future medical care.

- 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.

- Patients with other malignancies diagnosed within 2 years prior to study day-13
(except skin squamous or basal cell carcinoma).

- Active uncontrolled bacterial, viral or fungal infections.

- History of stroke within 6 months.

- Myocardial infarction within the past 6 months prior to study day 1, or has New York
Heart Association (NYHA) class III or IV heart failure or arrhythmias, unstable
angina, uncontrolled congestive heart failure or arrhythmias, or electrocardiographic
evidence of acute ischemia or active conduction system abnormalities. Prior to study
entry, any electrocardiography (ECG) abnormality at screening must be documented by
investigator as not medically relevant.

- A prior allogeneic transplant.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- Patient has received other investigational drugs within 3 weeks before enrollment.

- Hypersensitivity to bendamustine.

- Prior known refractoriness to bendamustine.