This phase II trial studies how well a donor stem cell transplant, treosulfan, fludarabine, and total-body irradiation work in treating patients with blood cancers (hematological malignancies). Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.
OUTLINE: Patients are assigned to 1 of 2 arms. ARM A (HIGH DOSE TREOSULFAN): Patients receive high dose treosulfan intravenously (IV) over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation on day -1 and allogeneic hematopoietic stem cell transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3-4. Beginning on day 5, patients receive cyclosporine IV twice daily (BID) or three times daily (TID) over 1-2 hours or orally (PO) (after 3 months, in the absence of GVHD, cyclosporine tapering will start by 5-10% per week, until drug withdrawal at 6 months post-transplant). Beginning on day 5, patients also receive mycophenolate sodium PO TID or mycophenolate mofetil IV or PO TID until day 35 (may be continued if active GVHD is present). Beginning on day 5, patients also receive filgrastim until the absolute neutrophil count is \> 1,000/uL for 3 consecutive days. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and computed tomography (CT) or positron emission tomography (PET)/CT on study. ARM B (LOW DOSE TREOSULFAN): Patients receive low dose treosulfan IV over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation and allogeneic hematopoietic stem cell transplantation, and receive cyclophosphamide, cyclosporine, mycophenolate sodium or mycophenolate mofetil, and filgrastim as in Arm A. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and CT or PET/CT on study. After completion of transplant, patients are followed up at 28, 56, 84, 365, and 730 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Undergo allogeneic hematopoietic stem cell transplantation
Given IV
Given IV or PO
Given IV
Given IV
Given IV or PO
Given PO
Undergo total-body irradiation
Given IV
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo echocardiography
Undergo blood sample collection
Undergo CT or PET/CT
Undergo PET/CT
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGGraft failure/rejection
The analysis for graft failure will be conducted among all patients as well as separately among patients by Arm A versus Arm B.
Time frame: Up to 2 years post-transplant
Overall survival
Time frame: At 1 and 2 years post-transplant
Progression free survival
Defined as the probability of being alive without sign of disease relapse or progression. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: At 1 year post-transplant
Non-relapse mortality
Defined as death from any cause without sign of disease progression or relapse. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: At day 100 and 1 year post-transplant
Relapse
Time frame: At 1 and 2 years post-treatment
Acute graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: Up to 2 years post-transplant
Chronic graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: Up to 2 years post-transplant
Clinically significant infections
Clinically significant infections include infections that have a significant impact on patient's clinical recovery, for instance infections that require in-patient hospitalization or prolongs existing hospitalization. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: Up to 2 years post-transplant
Platelet engraftment
Defined as the first of three consecutive days with platelet count \>= 20,000/uL on the peripheral blood, without platelet transfusion in the previous seven days. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time frame: At day 100 post-transplant
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