Comparing Peripheral Blood Stem Cell Transplantation Versus Bone Marrow Transplantation in Individuals With Hematologic Cancers - Full Text View

Purpose

The study is designed as a Phase III, randomized, open label, multicenter, prospective, comparative trial of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) versus marrow from unrelated donors for transplantation in patients with hematologic malignancies. Recipients will be stratified by transplant center and disease risk and will be randomized to either the PBSC or marrow arm in a 1:1 ratio.

Condition	Intervention	Phase
Acute Leukemia Chronic Leukemia Chronic Myeloproliferative Disorders Myelodysplastic and Myeloproliferative Disease	Biological: allogeneic bone marrow transplantation Biological: peripheral blood stem cell transplantation	Phase III

MedlinePlus related topics:

Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

ChemIDplus related topics:

Granulocyte colony-stimulating factor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Official Title:	A Phase III Randomized, Multicenter Trial Comparing G-CSF Mobilized Peripheral Blood Stem Cell With Marrow Transplantation From HLA Compatible Unrelated Donors (BMT CTN #0201)

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Two-year survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Survival [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
neutrophil engraftment [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
Patient quality of life [ Time Frame: Baseline, 6 months, 1, 2 and 5 years ] [ Designated as safety issue: No ]
platelet engraftment [ Time Frame: Day 100, 6 and 12 months ] [ Designated as safety issue: No ]
graft failure [ Time Frame: 28 and 100 days ] [ Designated as safety issue: Yes ]
acute graft-versus-host disease (GVHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
chronic GVHD [ Time Frame: 6 months 1, 2 and 3 years ] [ Designated as safety issue: No ]
time off all immunosuppressive therapy [ Time Frame: 2, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months ] [ Designated as safety issue: No ]
relapse [ Time Frame: 6, 12, 24 and 36 months ] [ Designated as safety issue: No ]
infections [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
grades III-IV unexpected adverse events [ Time Frame: 1,2 and 3 years ] [ Designated as safety issue: Yes ]
immune reconstitution [ Time Frame: 100 days, 6 months, 1 and 2 years ] [ Designated as safety issue: No ]
Donor quality of life [ Time Frame: 1, 6 and 12 months ] [ Designated as safety issue: No ]
Donor recovery to baseline toxicity scores [ Time Frame: 1, 6 and 12 months ] [ Designated as safety issue: No ]
Donor recovery of baseline CBC and WBC differential [ Time Frame: 1,6,12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	550
Study Start Date:	January 2004
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator allogeneic bone marrow transplantation	Biological: allogeneic bone marrow transplantation unrelated donor bone marrow transplant
2: Active Comparator peripheral blood stem cell transplantation	Biological: peripheral blood stem cell transplantation unrelated donor peripheral blood transplant

Detailed Description:

BACKGROUND:

Many studies of allogeneic marrow transplantation have shown that a higher dose of marrow cells correlates with more robust hematopoietic engraftment and lower mortality from infectious complications. Peripheral blood stem cells (PBSC) collected after mobilization with granulocyte colony stimulating factor (G-CSF) contain a larger number of CD34-positive (CD34) progenitors and total cells than bone marrow. These observations led to the hypothesis that transplantation of PBSC would lead to lower mortality compared to transplantation of marrow. In addition, PBSC grafts have a higher T cell content, predicting a possibly more powerful anti-leukemia effect. However, the higher T cell content of PBSC may also lead to increased incidence and severity of acute and chronic graft-versus-host disease (GVHD). This concern is especially serious when the donor is unrelated to the recipient. This prospective, randomized, multicenter clinical trial of unrelated donor transplantation will test the hypothesis that transplantation of PBSC leads to similar patient survival compared to transplantation of marrow.

DESIGN NARRATIVE:

This is a Phase III randomized, open label, multicenter clinical trial sponsored by the NMDP and the National Institutes of Health (NIH). The objective of the trial is to test the null hypothesis that there is no difference in overall survival after PBSC versus marrow transplants from HLA compatible unrelated donors. The study will compare G-CSF-mobilized PBSC transplantation with bone marrow transplantation from HLA-compatible unrelated donors for patients with leukemia, myelodysplastic or myeloproliferative syndromes. Conditioning and GVHD prophylaxis regimens will vary by center and within centers, however, the center must declare before randomization what regimens will be used for each patient. The primary endpoint of this trial is 2-year survival following randomization. Secondary analyses will consider neutrophil and platelet recovery, acute and chronic GVHD, time off all immunosuppressive therapy, relapse, infections, adverse events and immune reconstitution. The trial will include evaluation of patient and donor quality of life, composition of the graft, and immune reconstitution. Accrual is anticipated for 3 years with a follow-up period of 3 years.

Eligibility

Ages Eligible for Study:	up to 66 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Patient Inclusion Criteria:

One of the following diagnoses:

Acute myelogenous leukemia at the following stages: first remission, second remission, third or subsequent remission, or not in remission
Acute lymphoblastic leukemia at the following stages: first remission, second remission, third or subsequent remission, or not in remission
Chronic myelogenous leukemia at the following stages: chronic phase, accelerated phase, or blast phase
Myelodysplastic syndromes (MDS) at the following stages: refractory anemia; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; refractory cytopenia with multilineage dysplasia and ringed sideroblasts; refractory anemia with excess blasts-1 (5-10% blasts); refractory anemia with excess blasts-2 (10-20% blasts); myelodysplastic syndrome, unclassified; or MDS associated with isolated del (5q)
Myeloproliferative diseases: chronic myelomonocytic leukemia; agnogenic myeloid metaplasia with myelofibrosis (idiopathic myelofibrosis); juvenile myelomonocytic leukemia
Therapy-related AML or MDS with prior malignancy that has been in remission for at least 12 months. If the remission is less than 12 months, Medical Monitor or Protocol Chair approval is required for eligibility

Patient Exclusion Criteria:

Prior allogeneic or autologous transplants using any hematopoietic stem cell source; patients with secondary malignancies who have had a prior autologous transplant will be eligible; the prior autologous transplant must have been performed for the primary malignancy (such as lymphoma) and must have occurred 12 or more months prior to enrollment
Lymphoma (11% of 2001 NMDP transplants), other malignant disorders (6%), and non-malignant disorders (9%)

Donor Inclusion Criteria:

Matched for HLA-A, B, and DRB1 antigens
1. One antigen mismatch at HLA-A, B, or DRB1 is acceptable with or without mismatch at HLA-C
2. Typing is by DNA techniques: intermediate resolution for A, B, and C, and high resolution for DRB1. HLA-C typing is mandatory but will not count in the match.
Willing to undergo both bone marrow harvest and G-CSF administration with apheresis
Willing to be randomly assigned to either marrow or PBSC collection
Adequate peripheral venous access for leukapheresis or willing to undergo placement of a central catheter
Donor center affiliation with NMDP
Additional donor inclusion criteria can be found in the Donor Companion Manual

Donor Exclusion Criteria:

Pregnant (positive serum β-HCG) or uninterruptible breastfeeding
Known allergy to G-CSF or to E. Coli-derived recombinant protein products
History of autoimmune disorders
History of deep vein thrombosis or venous thromboembolism
History of iritis or episcleritis
History of serious adverse reaction to anesthesia
Thrombocytopenia (platelets less than 150,000 per mcL) at baseline evaluation
Current treatment with lithium
Presence of sickle hemoglobin as demonstrated by appropriate testing such as hemoglobin electrophoresis
Receiving experimental therapy or investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075816

Contacts


Contact: Mary Horowitz, MD		marymh@mcw.edu

Show 46 Study Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network

National Cancer Institute (NCI)

Investigators


Principal Investigator:	William Vaughan, MD	University of Alabama at Birmingham

Principal Investigator:	Auayporn Nademanee, MD	City of Hope National Medical Center

Principal Investigator:	Laura Johnston, MD	Stanford Hospital and Clinics

Principal Investigator:	Edward Ball, MD	UCSD Medical Center

Principal Investigator:	John Wingard, MD	University of Florida College of Medicine (Shands)

Principal Investigator:	Edmund Waller, MD	Emory University

Principal Investigator:	Margarida Silverman, MD	University of Iowa

Principal Investigator:	Jared Klein, MD	Loyola University

Principal Investigator:	Jan Jansen, MD	Indiana BMT at Beech Grove

Principal Investigator:	Corey Cutler, MD	DFCI/Brigham & Women's

Principal Investigator:	Saul Yanovich, MD	University of Maryland

Principal Investigator:	James Ferrara, MD	University of Michigan

Principal Investigator:	Shakila Khan, MD	Mayo Clinic

Principal Investigator:	Daniel Weisdorf, MD	University of Minnesota

Principal Investigator:	Joseph McGuirk, MD	Kansas City Cancer Centers

Principal Investigator:	John DiPersio, MD, PhD	Washington University/Barnes Jewish Hospital

Principal Investigator:	Shalini Shenoy, MD	Washington University/St. Louis Children's Hospital

Principal Investigator:	Nelson Chao, MD	Duke University

Principal Investigator:	David Hurd, MD	Wake Forest University

Principal Investigator:	Marcel Devetten, MD	University of Nebraska

Principal Investigator:	Scott Rowley, MD	Hackensack University Medical Center

Principal Investigator:	Joel Brochstein, MD	Hackensack University Medical Center

Principal Investigator:	Philip McCarthy, MD	Roswell Park Cancer Institute

Principal Investigator:	Indira Sahdev, MD	Schneider Children's Hospital

Principal Investigator:	Steven Devine, MD	Ohio State/Arthur G. James Cancer Hospital

Principal Investigator:	Hillard Lazarus, MD	University Hospitals of Cleveland/Case Western

Principal Investigator:	George Selby, MD	University of Oklahoma Medical Center

Principal Investigator:	Richard Maziarz, MD	Oregon Health Sciences University (Adult)

Principal Investigator:	H. Stacy Nicholson, MD	Oregon Health Sciences University (Peds)

Principal Investigator:	Steven Goldstein, MD	University of Pennsylvania

Principal Investigator:	Mounzer Agha, MD	University of Pittsburgh

Principal Investigator:	Haydar Frangoul, MD	Vanderbilt University

Principal Investigator:	Robert Krance, MD	Baylor College of Medicine/The Methodist Hospital

Principal Investigator:	Edward Agura, MD	Baylor University

Principal Investigator:	Paul Shaughnessy, MD	Texas Transplant Institute

Principal Investigator:	Paolo Anderlini, MD	University of Texas/MD Anderson CRC

Principal Investigator:	Michael Pulsipher, MD	Utah BMT/Primary Children's Medical Center

Principal Investigator:	Michael Pulsipher, MD	Utah BMT/University of Utah Medical School

Principal Investigator:	John McCarty, MD	Virginia Commonwealth University MCV Hospitals

Principal Investigator:	Ann Woolfrey, MD	Fred Hutchinson Cancer Research Center

Principal Investigator:	Robert Delage, MD	CHA Hopital Enfant-Jesus - Quebec

Principal Investigator:	Parveen Wasi, MD	Hamilton Health Sciences - McMaster Site

Principal Investigator:	Matthew Seftel, MD	CancerCare Manitoba BMT Program

Principal Investigator:	Stephen Couban, MD	Queen Elizabeth II Health Sciences Center - Halifax

Principal Investigator:	Lothar Huebsch, MD	Ottawa Hospital

Principal Investigator:	Laura Johnston, MD	Stanford Hospital and Clinics

Principal Investigator:	Bilijana Horn, MD	University of California, San Francisco

Principal Investigator:	Michael Nieder, MD	All Children's Hospital

Principal Investigator:	Serif Farag, MD, PhD	Indiana University School of Medicine

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Natonal Marrow Donor Program ( Lori Hanley )
Study ID Numbers:	418, BMTCTN-0201
First Received:	January 9, 2004
Last Updated:	October 7, 2008
ClinicalTrials.gov Identifier:	NCT00075816
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Study placed in the following topic categories:

Leukemia

Hematologic Neoplasms

Hematologic Diseases

Chronic Myeloproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms

Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 10, 2008

Sponsors and Collaborators:	National Heart, Lung, and Blood Institute (NHLBI) Blood and Marrow Transplant Clinical Trials Network National Cancer Institute (NCI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00075816