Peripheral Blood Stem Cell Transplant vs Bone Marrow Transplant in Individuals With Hematologic Cancers (BMT CTN 0201)

NCT ID: NCT00075816

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 551 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2014-04-30

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 National Marrow Donor Program (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.

Conditions

Leukemia; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bone Marrow Transplant

Allogeneic bone marrow transplantation

Group Type: ACTIVE_COMPARATOR

Allogeneic bone marrow transplantation

Intervention Type: BIOLOGICAL

Bone marrow transplant from HLA compatible unrelated donors.

Blood Stem Cell Transplant

Peripheral blood stem cell transplantation

Group Type: ACTIVE_COMPARATOR

Peripheral blood stem cell transplantation

Intervention Type: BIOLOGICAL

Peripheral blood transplant from HLA compatible unrelated donors.

Interventions

Allogeneic bone marrow transplantation

Bone marrow transplant from HLA compatible unrelated donors.

Intervention Type: BIOLOGICAL

Peripheral blood stem cell transplantation

Peripheral blood transplant from HLA compatible unrelated donors.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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 acute myelogenous leukemia (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

• 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

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%)

• 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

• Maximum Eligible Age: 66 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

UCSD Cancer Center

La Jolla, California, United States

University of California, San Francisco

San Francisco, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

University of Florida College of Medicine (Shands)

Gainesville, Florida, United States

Emory University

Atlanta, Georgia, United States

Loyola University

Maywood, Illinois, United States

IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Hospital

Kansas City, Kansas, United States

University of Maryland

Baltimore, Maryland, United States

DFCI/Brigham & Women's

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Washington University/Barnes Jewish Hospital

St Louis, Missouri, United States

Washington University/St. Louis Children's Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Cohen Children's Hospital

New Hyde Park, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Oregon Health & Science University (Peds)

Portland, Oregon, United States

Oregon Health Sciences University

Portland, Oregon, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

Baylor University Medical Center

Dallas, Texas, United States

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, United States

University of Texas/MD Anderson CRC

Houston, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

Utah BMT/Primary Children's Medical Center

Salt Lake City, Utah, United States

Utah BMT/University of Utah Medical School

Salt Lake City, Utah, United States

Virginia Commonwealth University MCV Hospitals

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Tom Baker Cancer Centre, Calgary

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Hamilton Health Sciences - McMaster Site

Hamilton, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

University of Toronto, Princess Margaret Hospital

Toronto, Ontario, Canada

Queen Elizabeth II Health Sciences Centre - Halifax

Halifax, , Canada

Countries

United States; Canada

References

Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, Ehninger G, Johnston L, Maziarz RT, Pulsipher MA, Porter DL, Mineishi S, McCarty JM, Khan SP, Anderlini P, Bensinger WI, Leitman SF, Rowley SD, Bredeson C, Carter SL, Horowitz MM, Confer DL; Blood and Marrow Transplant Clinical Trials Network. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012 Oct 18;367(16):1487-96. doi: 10.1056/NEJMoa1203517.

Reference Type: RESULT

PMID: 23075175 (View on PubMed)

Foley B, Cooley S, Verneris MR, Curtsinger J, Luo X, Waller EK, Anasetti C, Weisdorf D, Miller JS. Human cytomegalovirus (CMV)-induced memory-like NKG2C(+) NK cells are transplantable and expand in vivo in response to recipient CMV antigen. J Immunol. 2012 Nov 15;189(10):5082-8. doi: 10.4049/jimmunol.1201964. Epub 2012 Oct 17.

Reference Type: RESULT

PMID: 23077239 (View on PubMed)

Switzer GE, Bruce JG, Harrington D, Haagenson M, Drexler R, Foley A, Confer D, Bishop M, Anderlini P, Rowley S, Leitman SF, Anasetti C, Wingard JR. Health-related quality of life of bone marrow versus peripheral blood stem cell donors: a prespecified subgroup analysis from a phase III RCT-BMTCTN protocol 0201. Biol Blood Marrow Transplant. 2014 Jan;20(1):118-27. doi: 10.1016/j.bbmt.2013.10.024. Epub 2013 Nov 1.

Reference Type: RESULT

PMID: 24184336 (View on PubMed)

Waller EK, Logan BR, Harris WA, Devine SM, Porter DL, Mineishi S, McCarty JM, Gonzalez CE, Spitzer TR, Krijanovski OI, Linenberger ML, Woolfrey A, Howard A, Wu J, Confer DL, Anasetti C. Improved survival after transplantation of more donor plasmacytoid dendritic or naive T cells from unrelated-donor marrow grafts: results from BMTCTN 0201. J Clin Oncol. 2014 Aug 1;32(22):2365-72. doi: 10.1200/JCO.2013.54.4577. Epub 2014 Jun 30.

Reference Type: RESULT

PMID: 24982459 (View on PubMed)

Khera N, Majhail NS, Brazauskas R, Wang Z, He N, Aljurf MD, Akpek G, Atsuta Y, Beattie S, Bredeson CN, Burns LJ, Dalal JD, Freytes CO, Gupta V, Inamoto Y, Lazarus HM, LeMaistre CF, Steinberg A, Szwajcer D, Wingard JR, Wirk B, Wood WA, Joffe S, Hahn TE, Loberiza FR, Anasetti C, Horowitz MM, Lee SJ. Comparison of Characteristics and Outcomes of Trial Participants and Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 Trial. Biol Blood Marrow Transplant. 2015 Oct;21(10):1815-22. doi: 10.1016/j.bbmt.2015.06.004. Epub 2015 Jun 11.

Reference Type: RESULT

PMID: 26071866 (View on PubMed)

Young JH, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, Knust K, Horowitz MM, Confer DL, Dubberke ER, Pergam SA, Marty FM, Strasfeld LM, Brown JWM, Langston AA, Schuster MG, Kaul DR, Martin SI, Anasetti C; Blood and Marrow Transplant Clinical Trials Network Trial 0201. Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors. Biol Blood Marrow Transplant. 2016 Feb;22(2):359-370. doi: 10.1016/j.bbmt.2015.09.013. Epub 2015 Sep 25.

Reference Type: RESULT

PMID: 26409243 (View on PubMed)

Burns LJ, Logan BR, Chitphakdithai P, Miller JP, Drexler R, Spellman S, Switzer GE, Wingard JR, Anasetti C, Confer DL; Blood and Marrow Transplant Clinical Trials Network. Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Recovery of Unrelated Donors of Bone Marrow: A Prespecified Analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network Protocol 0201. Biol Blood Marrow Transplant. 2016 Jun;22(6):1108-1116. doi: 10.1016/j.bbmt.2016.02.018. Epub 2016 Mar 21.

Reference Type: RESULT

PMID: 27013014 (View on PubMed)

Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, Waller EK, Maziarz RT, Wu J, Shaw BE, Confer D, Horowitz MM, Anasetti C. Comparison of Patient-Reported Outcomes in 5-Year Survivors Who Received Bone Marrow vs Peripheral Blood Unrelated Donor Transplantation: Long-term Follow-up of a Randomized Clinical Trial. JAMA Oncol. 2016 Dec 1;2(12):1583-1589. doi: 10.1001/jamaoncol.2016.2520.

Reference Type: DERIVED

PMID: 27532508 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

U01HL069294-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMT CTN 0201

Identifier Type: OTHER

Identifier Source: secondary_id

5U24CA076518

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN0201

Identifier Type: -

Identifier Source: org_study_id

NCT00321776

Identifier Type: -

Identifier Source: nct_alias

NCT00473395

Identifier Type: -

Identifier Source: nct_alias