This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.
PRIMARY OBJECTIVES: I. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100. SECONDARY OBJECTIVES: I. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS). II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD. OUTLINE: This is a dose-escalation study of melphalan hydrochloride. CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo total body irradiation (TBI) on day -1. STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and tacrolimus IV and then orally (PO) once tolerated on days 5-180 with a taper beginning on day 100. After completion of study treatment, patients are followed up for 12 months and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Undergo allogeneic hematopoietic stem cell transplant
Given IV
Given IV
Correlative studies
Given IV
Given IV
Given IV and PO
Undergo TBI
Roswell Park Cancer Institute
Buffalo, New York, United States
Extensive Chronic Graft Versus Host Disease (GVHD)
Percentage of chronic GVHD of response by human leukocyte antigen (HLA) matching by cohort
Time frame: Up to 365 days
Clinical Response Assessed as Per Bone Marrow Transplant (BMT) Standard of Care
Patients who achieved a clinical response will be summarized descriptively using frequency counts
Time frame: Up to 4 years
Cumulative Incidence of Grade III-IV Acute Graft Versus Host Disease (GVHD)
Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.
Time frame: Up to 4 years
Cumulative Incidence of Relapse
Will be analyzed in a descriptive fashion with frequency counts.
Time frame: Up to 4 years
Engraftment Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care
Will be analyzed in a descriptive fashion with frequency counts.
Time frame: Up to 4 years
Overall Survival Assessed as Per Bone Marrow Transplant (BMT) Standard of Care
Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.
Time frame: Up to 4 years
1-Year Progression Free Survival (PFS) Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care
Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.
Time frame: At 1 year
Treatment-related Mortality Rates
Count of participants that died by cohort.
Time frame: All-Cause Mortality monitored/assessed up to 4 years. Adverse Events monitored/assessed from the start date of the conditioning regimen (Day -5) until 30 days after stem cell infusion will be reported, up to 12 months.
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