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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)


Phase 3
N/A
66 Years
Open (Enrolling)
Both
Leukemia, Myeloproliferative Disorders, Myelodysplastic-Myeloproliferative Diseases

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Trial Information

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)


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Two-year survival

Outcome Time Frame:

Measured at 2 years

Safety Issue:

No

Principal Investigator

William Vaughan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham

Authority:

United States: Federal Government

Study ID:

418

NCT ID:

NCT00075816

Start Date:

January 2004

Completion Date:

April 2014

Related Keywords:

  • Leukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases
  • Leukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Mayo Clinic Cancer CenterRochester, Minnesota  55905
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Schneider Children's HospitalNew Hyde Park, New York  11042
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
City of Hope National Medical CenterLos Angeles, California  91010
Baylor University Medical CenterDallas, Texas  75246
University of MinnesotaMinneapolis, Minnesota  55455
University of California, San FranciscoSan Francisco, California  94143
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Vanderbilt UniversityNashville, Tennessee  37232-6305
Duke University Medical CenterDurham, North Carolina  27710
University of Michigan Medical CenterAnn Arbor, Michigan  48104-0914
Oregon Health Sciences UniversityPortland, Oregon  
Emory UniversityAtlanta, Georgia  30322
University of MarylandBaltimore, Maryland  21201
Texas Transplant InstituteSan Antonio, Texas  78229
UCSD Cancer CenterLa Jolla, California  92093-0064
Loyola UniversityMaywood, Illinois  60153
Stanford Hospital and ClinicsStanford, California  94305
University of Florida College of Medicine (Shands)Gainesville, Florida  32610
Washington University/Barnes Jewish HospitalSt. Louis, Missouri  63110
Washington University/St. Louis Children's HospitalSt. Louis, Missouri  63110
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
University of Texas/MD Anderson CRCHouston, Texas  77030
Utah BMT/Primary Children's Medical CenterSalt Lake City, Utah  84132
Indiana BMT at Beech GroveBeech Grove, Indiana  46107
University of Kansas HospitalKansas City, Kansas  66160
DFCI/Brigham & Women'sBoston, Massachusetts  02114
Ohio State/Arthur G. James Cancer HospitalColumbus, Ohio  43210
University of Oklahoma Medical CenterOklahoma City, Oklahoma  73104
Oregon Health & Science University (Peds)Portland, Oregon  97239-3098
Baylor College of Medicine/The Methodist HospitalHouston, Texas  77030-2399
Utah BMT/University of Utah Medical SchoolSalt Lake City, Utah  84132
Virginia Commonwealth University MCV HospitalsRichmond, Virginia  23298-0037