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

Phase 2CompletedNCT01701986

M.D. Anderson Cancer Center64 enrolled

Overview

This phase I/II trial studies the side effects and best dose of gemcitabine hydrochloride, clofarabine, and busulfan before donor stem cell transplant and to see how well it works in treating patients with B-cell or T-cell non-Hodgkin lymphoma or Hodgkin lymphoma that does not respond to treatment. Giving chemotherapy before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

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.

Interventions

Allogeneic Bone Marrow TransplantationPROCEDURE

Undergo allogeneic BMT

Allogeneic Hematopoietic Stem Cell TransplantationPROCEDURE

Undergo allogeneic BMT or PBSCT

Anti-Thymocyte GlobulinBIOLOGICAL

Given IV

BusulfanDRUG

Given IV

ClofarabineDRUG

Given IV

Gemcitabine HydrochlorideDRUG

Given IV

Mycophenolate MofetilDRUG

Given IV then PO

Peripheral Blood Stem Cell TransplantationPROCEDURE

Undergo allogeneic PBSCT

Pharmacological StudyOTHER

Correlative studies

RituximabBIOLOGICAL

Given IV

TacrolimusDRUG

Given IV then PO

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Optimal Dose of Gemcitabine Hydrochloride Determined by Dose Limiting Toxicity

Dose limiting toxicity is defined as number of participants experienced grade 3-4 mucositis lasting for more than 3 days at peak severity, grade 3-4 skin toxicity lasting for more than 3 days at peak severity, occurring within 30 days from transplant, or grade 4 nonhematological/noninfectious toxicity.

Time frame: Within 30 days of transplant

Number of Participants That Had 100 Day Success Rate Post Transplant

Number of participants that are alive, engrafted, without grade 3-4 GVHD within 100 days post transplant.

Time frame: 100 days post transplant

Secondary Outcomes

Overall Survival

Number of participants that are still alive 5 years post transplant.

Time frame: Up to 5 years

Treatment Related Mortality

Number of participants that expired from transplant other than disease relapse within the first 100 days post transplant.

Time frame: Up to 100 days post-transplant

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes