Gemcitabine Hydrochloride, Clofarabine, and Busulfan Before Donor Stem Cell Transplant in Treating Patients With Refractory B-Cell or T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To define the maximum tolerated dose (MTD) of infusional gemcitabine (gemcitabine hydrochloride) combined with fixed doses of clofarabine and busulfan in patients with lymphoma receiving an allogeneic stem-cell transplant (alloSCT).

II. To estimate the day +100 success rate, defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-versus (vs.)-host-disease (GVHD).

SECONDARY OBJECTIVES:

I. To estimate the day +100 success rate (defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-vs.-host-disease [GVHD]).

II. To estimate the rate of event-free (EFS). III. To estimate the rate of overall survival (OS). IV. To estimate the response rate (RR) (defined as # of responses / # of patients with measurable tumors).

V. To estimate the complete response (CR) rate (defined as # of complete responses / # of patients with measurable tumors).

VI. To estimate the incidence of grade 2-4 and grade 3-4 acute GVHD. VII. To estimate the incidence of limited and extensive chronic GVHD.

OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride followed by a phase II study.

PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride intravenously (IV) over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with cluster of differentiation (CD)20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.

TRANSPLANT: Patients undergo allogeneic bone marrow (BMT) or peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO). Beginning on day 0, patients receive mycophenolate mofetil IV over 2 hours or PO thrice daily (TID).

After completion of study treatment, patients are followed up at 3, 6, and 12 months, and then every 6 months for 4 years.

Inclusion criteria

• Patients with refractory B-cell or T-cell non-Hodgkin's lymphoma or Hodgkin's lymphoma who are eligible for allogeneic transplantation
• An 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1) sibling or unrelated donor
• Left ventricular ejection fraction (EF) >= 45%
• Forced expiratory volume in one second (FEV1) >= 50%
• Forced vital capacity (FVC) >= 50%
• Diffusing capacity of the lung for carbon monoxide (DLCO) >= 50%
• Estimated serum creatinine clearance >= 50 ml/min (using the Cockcroft-Gault formula)
• Serum creatinine =< 1.6 mg/dL
• Serum bilirubin =< 2 x upper limit of normal
• Serum glutamate pyruvate transaminase (SGPT) =< 2 x upper limit of normal
• Voluntary signed 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
• Pregnancy (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
• Active hepatitis B, either active carrier (hepatitis B virus surface antigen [HBsAg] +) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL)
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
• Human immunodeficiency virus (HIV) infection
• Active uncontrolled bacterial, viral or fungal infections
• Exposure to other investigational drugs within 2 weeks before enrollment
• Grade >= 3 non-hematologic toxicity from previous therapy that has not resolved to =< grade 1
• Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
• Prior whole brain irradiation
• Prior autologous stem-cell transplant (SCT) in the prior 3 months