Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
This phase II trial is studying 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 therapy of the patient's disease than using bone marrow.
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Radiation: total-body irradiation
Procedure: laboratory biomarker analysis
|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|
- 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.
- Incidence of chronic GVHD [ Time Frame: Up to day 90 ] [ Designated as safety issue: No ]Scored according to the National Cancer Institute (NCI) criteria. The time to onset of limited and extensive chronic GVHD will be recorded.
- Cumulative incidence of NRM, defined as death without evidence of disease progression [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- 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.
- 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.
- 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 (STR)-polymerase chain reaction (PCR) on peripheral blood sorted into CD3 and CD33 cell fractions.
- 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.
- 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.
- 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%.
- 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.
- Infections [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]Reported by anatomic site, date of onset, organism and resolution, if any.
- Toxicity of treatment regimen [ Time Frame: Up to day 90 ] [ Designated as safety issue: Yes ]Assessed by Common Terminology Criteria for Adverse Events (CTCAE) 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.
Drug: fludarabine phosphate
Other Names:Drug: cyclophosphamide
Other Names:Drug: tacrolimus
Given IV or PO
Other Names:Drug: mycophenolate mofetil
Other Names:Biological: filgrastim
Given IV or SC
Other Names:Procedure: peripheral blood stem cell transplantation
Other Names:Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo PBSCRadiation: total-body irradiation
Undergo total-body irradiation
Other Name: TBIProcedure: laboratory biomarker analysis
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 (NRM) 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|