This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.
PRIMARY OBJECTIVES: I. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem cells for nonmyeloablative transplants from related, haploidentical donors will not result in unacceptable rates of high-grade acute or chronic GVHD, non-relapse mortality or relapse compared to historical data on nonmyeloablative transplants from unrelated donors. SECONDARY OBJECTIVES: I. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell (RBC) and platelet transfusions, incidences of graft failure, transplant-related toxicities, disease-free survival and overall survival. OUTLINE: Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice daily (BID) on days 5-180 (may be continued if active GVHD is present), mycophenolate mofetil IV or PO thrice daily (TID) on days 5-35 (may be continued if GVHD present), and filgrastim IV beginning on day 5 until the absolute neutrophil count (ANC) is \>= 1,000/mm\^3 for three consecutive days. Treatment continues in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Given IV
Given SQ
Given IV
Given PO
Undergo PBSC
Undergo PBSC
Given IV or PO
Undergo total-body irradiation (TBI)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Non-relapse Mortality at 1 Year
Cumulative incidence of death without evidence of disease progression at 1 year
Time frame: Up to 1 year
Percentage of Participants With Chronic Graft Versus Host Disease
Scored according to the National Cancer Institute criteria. Mild-to-severe chronic GVHD at 2 years.
Time frame: Up to 2 years post-transplant
Incidence of Grades III/IV Acute Graft Versus Host Disease
Grading determined by organ system stages. Grade III/IV acute graft versus host disease is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.
Time frame: At day 84
Relapse of Malignancy After Transplantation
Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.
Time frame: Up to 7 years
Time to Neutrophil Recovery
Achievement of an absolute neutrophil count greater or equal to 500/mm\^3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.
Time frame: Up to day 84 post-transplant
Time to Platelet Recovery
The first day of a sustained platelet count \> 20,000/mm\^3 with no platelet transfusions in the preceding seven days.
Time frame: Up to day 84 post-transplant
Incidence of Primary Graft Failure
Defined as \< 5% donor CD3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.
Time frame: At day 84
Disease-free Survival
Defined as being alive and in remission by \< 5% blasts by bone marrow morphology for patients with myeloid malignancies and CT or PET imaging for patients with lymphoid malignancies at the time of the assessment
Time frame: 3 years from the date of transplant
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System
Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 was determined.
Time frame: Up to day 90
Number of Red Blood Cell Transfusions
Number of units of RBCs given to the patient between day 0 and day 100 post transplant
Time frame: Day 0-100
Number of Platelet Transfusions
Number platelet transfusions given to the patient between day 0 and day 100 post transplant
Time frame: Day 0-100
Point Estimate of Overall Survival at 3 Years
Kaplan Meier estimate of the percentage of participants with overall survival at 3 years
Time frame: 3 years
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