This phase II trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor 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. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) before the transplant may help increase this effect.
PRIMARY OBJECTIVES: I. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it with that of the initial 2 Step RIC regimen. SECONDARY OBJECTIVES: I. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this treatment protocol. II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen. III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial. IV. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial. OUTLINE: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -15 to -12, busulfan IV on days -14 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -10. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV twice daily (BID) on days -1 to 28. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Given IV
Given IV
Undergo TBI
Undergo DLI
Given IV
Undergo allogeneic PBSCT
Undergo allogeneic PBSCT
Given IV
Given IV
Correlative studies
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Disease-free Survival (DFS)
This hypothesis will be rejected if the 95% confidence interval for year DFS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.
Time frame: 1 year post hematopoietic stem cell transplant (HSCT)
Overall Survival
Will be analyzed and reported descriptively.
Time frame: 1 year post HSCT
Overall Survival
Will be analyzed and reported descriptively.
Time frame: 3 years post HSCT
Immune Reconstitution at Day +28
CD4 and CD8 values at Day +28. Reported as mean (standard deviation).
Time frame: Up to 1 year
Immune Reconstitution at Day +90
CD4 and CD8 values at Day +90. Reported as mean (standard deviation).
Time frame: Up to 1 year
Incidence and Degree of Graft Versus Host Disease
The incidence and severity of graft-versus-host disease (GVHD) will be analyzed and reported descriptively. Clinical manifestations including skin rash, diarrhea, and liver function test abnormalities will be assessed. GVHD will be staged using established clinical grading systems: acute GVHD will be graded according to the modified Glucksberg criteria, and chronic GVHD will be graded using the NIH consensus criteria. These grading systems classify GVHD severity based on organ involvement and clinical symptoms. Higher stages or grades reflect more severe disease and are considered worse outcomes.
Time frame: Up to 1 year
Engraftment Rates
Will be analyzed and reported descriptively.
Time frame: Up to 1 year
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