Targeted Marrow Irradiation, Fludarabine Phosphate, and Busulfan before Donor Progenitor Cell Transplant in Treating Patients with Hematologic Malignancies

Inclusion Criteria

• Patients ineligible to receive full myeloablative conditioning regimen for allogeneic hematopoietic progenitor cell transplant due to age or comorbidities
• Patients must have histologic or cytologic diagnosis of hematologic malignancies with an indication for allogeneic hematopoietic progenitor cell transplantation, who are ineligible to receive a full ablative conditioning regimen as part of their transplantation, including: * Acute myeloid leukemia (AML) ** As post-remission therapy in patients with intermediate and high risk cytogenetic and molecular abnormalities, including therapy-related leukemia ** Patients refractory to induction chemotherapy ** Relapsed after complete remission * Acute lymphocytic leukemia (ALL) ** As post remission therapy in Philadelphia chromosome positive (Ph+) and Philadelphia chromosome negative (Ph-) ALL in complete remission, with or without minimal residual disease in patients older than 55 years of age and those younger than 55 years but ineligible for treatment with fully ablative conditioning regimens ** Relapsed or refractory after prior therapy * Non Hodgkin lymphoma ** Aggressive lymphoma (Burkitt, diffuse large B cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma) relapsed after autologous hematopoietic progenitor transplantation or patients ineligible to receive autologous hematopoietic progenitor transplantation because of mobilization failure or persistent bone marrow involvement by lymphoma ** Indolent lymphoma (follicular, marginal zone lymphoma, mantle cell lymphoma, etc.) patients are eligible if they have received at least two lines of therapy and have remission of their extramedullary disease ** Indolent and aggressive lymphoma patients with refractory disease to at least two lines of therapy * Hodgkin lymphoma ** Patients relapsed after autologous hematopoietic progenitor transplantation with remission of at least their extramedullary disease after salvage therapy ** Patients with refractory disease to at least 2 lines of chemotherapy * Multiple myeloma ** Patients who have presented with relapsed or refractory disease after second line therapy * Myelodysplastic syndrome ** Patients with International Prognostic Score System Risk rating of: intermediate – 2 and higher, ineligible to receive a fully ablative conditioning regimen for allogeneic hematopoietic progenitor cell transplantation * Chronic lymphocytic leukemia ** Patients with disease relapsed or refractory after 2 or more lines of therapy, ineligible to receive fully ablative conditioning regimens for allogeneic hematopoietic progenitor cell transplantation ** Patients with disease transformed to aggressive lymphoma (Richter transformation) who have received induction therapy for their aggressive disease * Chronic myeloid leukemia: ** In chronic phase that has failed therapy with at least 3 different tyrosine kinase inhibitors or has progressed to accelerated or blast phase ** In accelerated or blast crisis * Myeloproliferative syndromes including myelofibrosis * Complete remission is not necessary for enrollment in this protocol, however Hodgkin and non Hodgkin lymphoma must have had remission of all extramedullary disease to be eligible to participate in this trial
• Patients must have an allogeneic hematopoietic progenitor cell donor (HPCT), either a matched sibling, mismatched (1 allele) sibling, or a matched unrelated donor (MUD) or a mismatched (1 allele) unrelated donor * Previous autologous hematopoietic progenitor cell transplantation is allowed; a minimum of 6 months should have elapsed from prior autologous hematopoietic progenitor cell transplantation; prior transplantation with conditioning regimens using total body irradiation is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of > 12 weeks, in the opinion of and as documented by the investigator
• Total bilirubin =< 1.5 times the institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine clearance (calculated by the Cockroft-Gault formula) >= 30 ml/min
• Pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], carbon monoxide diffusing capability [DLCO] >= 40%
• The effects of targeted marrow irradiation, fludarabine and busulfan on the developing human fetus are unknown. For this reason and because radiation therapy, purine analogs and alkylating agents as well as other therapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) from the time of study entry, for the duration of study participation and for 3 months after completing treatment. Should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior non-hematologic treatment toxicities must be resolved to =< grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, with the exception of the following grade 2 toxicities: alopecia; dry skin; spleen disorders, hearing impairment; tinnitus; hypothyroidism; hyperthyroidism; endocrine disorders; blurred vision; cataracts; constipation; gastroesophageal reflux; fatigue; abnormal coagulation tests international normalized ratio (INR) and/or activated partial thromboplastin time (aPTT); weight gain or weight loss; anorexia; glucose intolerance; hypoalbuminemia; hypokalemia; muscle weakness; dysgeusia; paresthesias; peripheral motor and/or sensory neuropathy; hot flashes; hypertension
• Patients must not have received other investigational agents within 14 days of initiation of the conditioning regimen
• Patients with untreated brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine and or busulfan or other agents used in this study
• Prior allogeneic hematopoietic progenitor cell transplantation
• Prior autologous hematopoietic progenitor cell transplantation if the conditioning regimen included total body irradiation
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; this exclusion criterion does not include the underlying disease for which the patient is undergoing hematopoietic progenitor cell transplantation
• Pregnant or breastfeeding women are excluded from this study. The cytotoxic therapeutic agents, fludarabine and busulfan, as well as ionizing radiation, have the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with fludarabine and busulfan, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with busulfan and fludarabine. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients with a history of treatment with radiation therapy are excluded
• Due to technical limitations of TMI, patients must be no taller than 1.9 m (6 feet 4 inches), and no wider from elbow to elbow in the supine position than 60 cm