Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
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ClinicalTrials.gov Identifier: NCT01028716 |
Recruitment Status :
Recruiting
First Posted : December 9, 2009
Last Update Posted : January 20, 2021
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Condition or disease | Intervention/treatment | Phase |
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Acute Biphenotypic Leukemia Acute Erythroid Leukemia in Remission Acute Leukemia in Remission Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia in Remission Acute Myeloid Leukemia With FLT3/ITD Mutation Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2); GATA2, MECOM Acute Myeloid Leukemia With Multilineage Dysplasia Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214 Acute Undifferentiated Leukemia Adult Acute Lymphoblastic Leukemia in Complete Remission B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1) B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 Burkitt Lymphoma Childhood Acute Lymphoblastic Leukemia in Complete Remission DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma Myelodysplastic Syndrome Recurrent Anaplastic Large Cell Lymphoma Blasts Under 5 Percent of Bone Marrow Nucleated Cells 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 Hematopoietic Cell Transplant Recipient | Drug: Cyclophosphamide Biological: Filgrastim Drug: Fludarabine Phosphate Procedure: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Peripheral Blood Stem Cell Transplantation Drug: Tacrolimus Radiation: Total-Body Irradiation Drug: Fludarabine | Phase 2 |
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 (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (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 |
Actual Study Start Date : | February 8, 2010 |
Estimated Primary Completion Date : | January 4, 2023 |
Estimated Study Completion Date : | January 4, 2023 |

Arm | Intervention/treatment |
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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 beginning on day 5 until the ANC is >= 1,000/mm^3 for three consecutive days.
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Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Filgrastim Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Procedure: Laboratory Biomarker Analysis Correlative studies Drug: Mycophenolate Mofetil Given PO
Other Names:
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Undergo PBSC
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation Undergo PBSC
Other Names:
Drug: Tacrolimus Given IV or PO
Other Names:
Radiation: Total-Body Irradiation Undergo total-body irradiation (TBI)
Other Names:
Drug: Fludarabine Given IV
Other Names:
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- Cumulative incidence of non-relapse mortality, defined as death without evidence of disease progression [ Time Frame: Up to 1 year ]
- Incidence of chronic graft versus host disease [ Time Frame: Up to 1 year post-transplant ]Scored according to the National Cancer Institute criteria. The time to onset of limited and extensive chronic graft versus host disease will be recorded.
- Incidence of grades III/IV acute graft versus host disease [ Time Frame: At day 84 ]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.
- Relapse of malignancy after transplantation [ Time Frame: Up to 7 years ]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 post-transplant ]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 ]Reported by anatomic site, date of onset, organism and resolution, if any.
- Neutrophil recovery [ Time Frame: Up to day 84 post-transplant ]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.
- Platelet recovery [ Time Frame: Up to day 84 post-transplant ]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: At day 84 ]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.
- Progression-free survival [ Time Frame: Time interval to relapse/recurrence, to death or to last follow-up, assessed for up to 7 years ]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 post-transplant ]Initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and absolute neutrophil count 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 ]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.

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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Molecular based human leukocyte antigen (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); 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); if the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has < 5% blasts, an exception may be made to include this patient up to principal investigator (PI) discretion
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Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following:
- Adverse cytogenetics including but not limited to 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
- Minimal residual disease
- Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation
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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
- French-American-British (FAB) M6 or M7 leukemia, or
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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)]
- Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation
- Acute leukemias in second (2nd) or subsequent remission
- Biphenotypic/undifferentiated leukemias in first (1st) or subsequent complete remission (CR)
- High-risk MDS status-post cytotoxic chemotherapy
- Burkitt's lymphoma: second or subsequent CR
- Chemotherapy-sensitive (at least stable disease) 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
- Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study
- 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
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01028716
Contact: Rachel B. Salit | 206-667-1317 | rsalit@fredhutch.org |
United States, Washington | |
VA Puget Sound Health Care System | Withdrawn |
Seattle, Washington, United States, 98101 | |
Fred Hutch/University of Washington Cancer Consortium | Recruiting |
Seattle, Washington, United States, 98109 | |
Contact: Rachel B. Salit 206-667-1317 rsalit@fredhutch.org | |
Principal Investigator: Rachel B. Salit |
Principal Investigator: | Rachel B. Salit | Fred Hutch/University of Washington Cancer Consortium |
Responsible Party: | Fred Hutchinson Cancer Research Center |
ClinicalTrials.gov Identifier: | NCT01028716 |
Other Study ID Numbers: |
2372.00 NCI-2009-01433 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2372 2372.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) P30CA015704 ( U.S. NIH Grant/Contract ) RG9213052 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
First Posted: | December 9, 2009 Key Record Dates |
Last Update Posted: | January 20, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Burkitt Lymphoma Lymphoma Leukemia Leukemia, Myeloid Multiple Myeloma Neoplasms, Plasma Cell Leukemia, Myeloid, Acute Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Mantle-Cell Hematologic Neoplasms Lymphoma, Large-Cell, Anaplastic Leukemia, Erythroblastic, Acute Leukemia, Biphenotypic, Acute |
Myelodysplastic Syndromes Syndrome Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Pathologic Processes Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders |