This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.
PRIMARY OBJECTIVES: I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity conditioning (RIC) approaches in the "vulnerable" population defined as: patients with hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores \>= 2, but no more than a score of 5 as based on the Sorror et al. data. SECONDARY OBJECTIVES: I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1 year for patients treated on this study to the that of patients undergoing haploidentical RIC hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed in the 2 step RIC trials. II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach. III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach. OUTLINE: RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to -8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6. TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV twice daily (BID) on days -1 to 28 in the absence of GVHD. After completion of study treatment, patients are followed up for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given IV
Undergo TBI
Undergo DLI
Given IV
Undergo PBSC transplant
Undergo PBSC transplant
Given PO
Given IV
Correlative studies
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Overall Survival (OS)
OS will be estimated using Kaplan-Meier curves. The 1-year OS rate and corresponding 95% confidence interval will be estimated from the Kaplan-Meier curve for the OS.
Time frame: At 1 year post HSCT
Relapse Related Mortality (RRM)
Will be reported descriptively. RRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
Time frame: At 1 year post HSCT
Non-Relapse Mortality (NRM)
Will be reported descriptively. NRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
Time frame: At 1 year post HSCT
Incidence and Severity of GVHD
Will be reported descriptively
Time frame: Up to 1 year post HSCT
Engraftment Rates
Will be reported descriptively
Time frame: Up to 1 year post HSCT
Lymphoid Reconstitution
Lymphoid reconstitution will be evaluated monthly to every other month during the first year post HSCT and will be reported descriptively.
Time frame: Up to 1 year post HSCT
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