|December 8, 2009
|February 7, 2013
|February 2017 (final data collection date for primary outcome measure)
- 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.
|Incidence of severe acute and chronic GvHD, nonrelapse-related deaths and relapse [ Time Frame: Day +84 ] [ Designated as safety issue: No ]
|Complete list of historical versions of study NCT01028716 on ClinicalTrials.gov Archive Site
- 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.
- Neutrophil recovery [ Designated as safety issue: No ]
- Primary graft failure [ Time Frame: Day +84 ] [ Designated as safety issue: No ]
- Secondary graft failure [ Designated as safety issue: No ]
- Platelet recovery [ Designated as safety issue: No ]
- Donor cell engraftment [ Time Frame: Day >= 84 after transplantation and day +28 ] [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Infections [ Designated as safety issue: Yes ]
- Toxicity as assessed by CTCAE version 3.0 [ Designated as safety issue: Yes ]
|Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
|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
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
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, nonrelapse 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 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.
|Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- 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
|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 twice daily 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
- Drug: cyclophosphamide
- Drug: tacrolimus
- Drug: mycophenolate mofetil
- Biological: filgrastim
- Procedure: peripheral blood stem cell transplantation
- Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
- Radiation: total-body irradiation
- Procedure: laboratory biomarker analysis
|February 2017 (final data collection date for primary outcome measure)
- Molecular based human leukocyte antigens (HLA) typing will be performed for the HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity; a minimum match of 5/10 is required
- An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor
- Acute leukemias (includes T lymphoblastic lymphoma) in remission
- Remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp)
Acute Lymphoblastic Leukemia in high risk first complete remission (CR1) as defined by at least one of the following:
- Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements
- White blood cell counts > 30,000/mcL
- Patients over 30 years of age
- Time to complete remission > 4 weeks
- Presence of extramedullary disease
Acute Myelogenous Leukemia in high risk CR1 as defined by at least one of the following:
- Greater than 1 cycle of induction therapy required to achieve remission
- Preceding myelodysplastic syndrome (MDS)
- Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities; or French-American-British (FAB) M6 or M7 leukemia
OR adverse cytogenetics for overall survival such as:
- Those associated with MDS
- Complex karyotype (>= 3 abnormalities); or
- Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)
- Acute Leukemias in 2nd or subsequent remission
- Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR
- High-risk MDS status-post cytotoxic chemotherapy
- Burkitt's lymphoma: second or subsequent CR
- Chemotherapy-sensitive (complete or partial response) large cell, Mantle Cell or Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant
- Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan)
- Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
- Left ventricular ejection fraction at rest must be >= 35%
- Bilirubin =< 2.5 mg/dL
- Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) < 5 x ULN
- Alkaline phosphatase < 5 x ULN
- Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or glomerular filtration rate [GFR]) > 40 mL/min/1.73m^2
- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 92% on room air
- Karnofsky/Lansky score >= 60%
- Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active GVHD requiring immunosuppressive therapy
- DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient; eligible donors include biological parents, siblings, or children, or half-siblings
- DONOR: Age >= 12 years
- DONOR: Weight >= 40 kg
- DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
- DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines
- HLA-matched or single allele-mismatched donor able to donate
- Pregnancy or breast-feeding
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
- Patients with primary idiopathic myelofibrosis
- DONOR: Positive anti-donor HLA antibody
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
|National Cancer Institute (NCI)
||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
|Fred Hutchinson Cancer Research Center