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

This Tabular View shows the required WHO registration data elements as marked by ^†

Tracking Information

First Received Date ^†

January 9, 2004

Last Updated Date

February 19, 2009

Start Date ^†

January 2004

Current Primary Outcome Measures ^†

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

Original Primary Outcome Measures ^†

Same as current

Change History

Complete list of historical versions of study NCT00075816 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^†

Survival [ Time Frame: Measured at 2 and 3 years ] [ Designated as safety issue: No ]
Neutrophil engraftment [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: No ]
Patient quality of life [ Time Frame: Measured at baseline, 6 months, and 1, 2, and 5 years ] [ Designated as safety issue: No ]
Platelet engraftment [ Time Frame: Measured at Day 100, and 6 and 12 months ] [ Designated as safety issue: No ]
Graft failure [ Time Frame: Measured at 28 and 100 days ] [ Designated as safety issue: Yes ]
Acute graft-versus-host disease (GVHD) [ Time Frame: Measured at 100 days ] [ Designated as safety issue: No ]
Chronic GVHD [ Time Frame: Measured at 6 months, and 1, 2, and 3 years ] [ Designated as safety issue: No ]
Time off all immunosuppressive therapy [ Time Frame: Measured at 2, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months ] [ Designated as safety issue: No ]
Relapse [ Time Frame: Measured at 6, 12, 24, and 36 months ] [ Designated as safety issue: No ]
Infections [ Time Frame: Measured at 1 and 2 years ] [ Designated as safety issue: No ]
Grades III-IV unexpected adverse events [ Time Frame: Measured at 1, 2, and 3 years ] [ Designated as safety issue: Yes ]
Immune reconstitution [ Time Frame: Measured at 100 days, 6 months, and 1 and 2 years ] [ Designated as safety issue: No ]
Donor quality of life [ Time Frame: Measured at 1, 6, and 12 months ] [ Designated as safety issue: No ]
Donor recovery to baseline toxicity scores [ Time Frame: Measured at 1, 6, and 12 months ] [ Designated as safety issue: No ]
Donor recovery of baseline CBC and WBC differential [ Time Frame: Measured at 1, 6, and 12 months ] [ Designated as safety issue: No ]

Original Secondary Outcome Measures ^†

Survival
incidences of neutrophil and platelet engraftment, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, time off all immunosuppressive therapy, relapse, infections, adverse events, immune reconstitution, and quality of life
time to return to baseline toxicity score
CBC and WBC differential values after donation
quality of life

Descriptive Information

Brief Title ^†

Comparing Peripheral Blood Stem Cell Transplantation Versus Bone Marrow Transplantation in Individuals With Hematologic Cancers

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)

Brief Summary

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.

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.

Study Phase

Phase III

Study Type ^†

Interventional

Study Design ^†

Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Condition ^†

Leukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases

Intervention ^†

Biological: Allogeneic bone marrow transplantation
Biological: Peripheral blood stem cell transplantation

Study Arms / Comparison Groups

Active Comparator: Allogeneic bone marrow transplantation
Active Comparator: Peripheral blood stem cell transplantation

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^†

Recruiting

Enrollment ^†

550

Estimated Completion Date

April 2012

Estimated Primary Completion Date

April 2011 (final data collection date for primary outcome measure)

Eligibility 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

Gender

Both

Ages

up to 66 Years

Accepts Healthy Volunteers

Contacts ^††

Contact: Mary Horowitz, MD

marymh@mcw.edu

Location Countries ^†

United States, Canada

Expanded Access Status

Administrative Information

NCT ID ^†

NCT00075816

Responsible Party

Lori Hanley, Natonal Marrow Donor Program

Secondary IDs ^††

BMTCTN-0201

Study Sponsor ^†

National Heart, Lung, and Blood Institute (NHLBI)

Collaborators ^††

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:	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:	Patrick J Stiff, 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:	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:	Laura M Rooms, MD	University of Oklahoma Medical Center
Principal Investigator:	Richard Maziarz, MD	Oregon Health Sciences University (Adult)
Principal Investigator:	Eneida Nemecek, MD	Oregon Health Sciences University (Peds)
Principal Investigator:	Steven Goldstein, MD	University of Pennsylvania
Principal Investigator:	Mounzer Agha, MD	University of Pittsburgh
Principal Investigator:	Adetola Kassim, 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
Principal Investigator:	David E Avigan, MD	Beth Israel Deaconess Medical Center
Principal Investigator:	Cindy Toze, MD	British Columbia Children's Hospital, Vancouver
Principal Investigator:	Robert Delage, MD	CHA Hopital Enfant-Jesus, Quebec
Principal Investigator:	Jeffrey Schiber, MD	City of Hope Samaritan
Principal Investigator:	Jean Roy, MD	Hopital Maisonneuve-Rosemont, Montreal
Principal Investigator:	Joseph McGuirk, MD	University of Kansas Hospital
Principal Investigator:	Jeffrey Lipton, M.D., Ph.D.	University of Toronto, Princess Margaret Hospital
Principal Investigator:	Clayton Smith, Md	Vancouver General Hospital
Principal Investigator:	Lynn Savoie, MD	Tom Baker Cancer Centre, Calgary
Principal Investigator:	Kellie A Sprague, MD	Tufts Medical Center

Information Provided By

National Heart, Lung, and Blood Institute (NHLBI)

Verification Date

February 2009

^† Required WHO trial registration data element.
^†† WHO trial registration data element that is required only if it exists.