Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
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.
Acute Erythroid Leukemia in Remission
Acute Leukemia in Remission
Acute Megakaryoblastic Leukemia
Acute Myeloid Leukemia in Remission
Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Complete Remission
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Recurrent Anaplastic Large Cell Lymphoma
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Follicular Lymphoma
Recurrent Hodgkin Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Secondary Acute Myeloid Leukemia
T Lymphoblastic Lymphoma
Drug: Fludarabine Phosphate
Procedure: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Procedure: Peripheral Blood Stem Cell Transplantation
Radiation: Total-Body Irradiation
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source|
- Cumulative incidence of non-relapse mortality, defined as death without evidence of disease progression [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- Incidence of chronic GVHD [ Time Frame: Up to day 90 ] [ Designated as safety issue: No ]Scored according to the National Cancer Institute criteria. The time to onset of limited and extensive chronic GVHD will be recorded.
- Incidence of grades III/IV acute GVHD [ Time Frame: At day 84 ] [ Designated as safety issue: No ]Grading determined by organ system stages. Grade III/IV acute GVHD is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.
- Relapse of malignancy after transplantation [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]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.
- Donor cell engraftment [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]Donor chimerism in the T-cell (CD3-positive) and granulocyte (CD33-positive) fractions of sorted peripheral blood greater or equal to 50%.
- Infections [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]Reported by anatomic site, date of onset, organism and resolution, if any.
- Neutrophil recovery [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]Achievement of an ANC 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.
- Platelet recovery [ Time Frame: Up to day 84 post-transplant ] [ Designated as safety issue: No ]The first day of a sustained platelet count > 20,000/mm^3 with no platelet transfusions in the preceding seven days.
- Primary graft failure [ Time Frame: Day 84 ] [ Designated as safety issue: No ]Defined as < 5% donor cluster of differentiation (CD)3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.
- Progression-free survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]Defined as the minimum time interval to relapse/recurrence, to death or to last follow-up.
- Secondary graft failure [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]Initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and ANC is less than 500/mm^3, then it will be counted as a secondary graft failure.
- Toxicity of treatment regimen [ Time Frame: Up to day 90 ] [ Designated as safety issue: Yes ]Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 will be determined.
|Study Start Date:||February 2010|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (nonmyeloablative HCT, TBI)
Patients receive fludarabine 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 PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV or SC beginning on day 5 until the ANC is >= 1,000/mm^3 for three consecutive days.
Other Names:Biological: Filgrastim
Given IV or SC
Other Names:Drug: Fludarabine Phosphate
Other Names:Procedure: Laboratory Biomarker Analysis
Correlative studiesDrug: Mycophenolate Mofetil
Other Names:Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Other Names:Procedure: Peripheral Blood Stem Cell Transplantation
Other Names:Drug: Tacrolimus
Given IV or PO
Other Names:Radiation: Total-Body Irradiation
Undergo total-body irradiation
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.
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.
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 or subcutaneously (SC) 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01028716
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Rachel B. Salit 206-667-1317|
|Principal Investigator: Rachel B. Salit|
|Principal Investigator:||Rachel Salit||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|