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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075816
• Other study ID #: BMTCTN0201
• Secondary ID: U01HL069294-05BM
• Status: Completed
• Phase: Phase 3
• Start date: January 2004
• Est. completion date: April 2014

Study information

• Verified date: December 2022
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00321776
• NCT00473395

Recruitment information / eligibility

• Status: Completed
• Enrollment: 551
• Est. completion date: April 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 66 Years

Eligibility

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 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

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 ß-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

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic-Myeloproliferative Diseases
• Myeloproliferative Disorders

Intervention

Biological:
• Allogeneic bone marrow transplantation
Bone marrow transplant from HLA compatible unrelated donors.
• Peripheral blood stem cell transplantation
Peripheral blood transplant from HLA compatible unrelated donors.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre, Calgary	Calgary	Alberta
Canada	Queen Elizabeth II Health Sciences Centre - Halifax	Halifax
Canada	Hamilton Health Sciences - McMaster Site	Hamilton	Ontario
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	University of Toronto, Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	DFCI/Brigham & Women's	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Ohio State/Arthur G. James Cancer Hospital	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida College of Medicine (Shands)	Gainesville	Florida
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Baylor College of Medicine/The Methodist Hospital	Houston	Texas
United States	University of Texas/MD Anderson CRC	Houston	Texas
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	UCSD Cancer Center	La Jolla	California
United States	Loyola University	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University	Nashville	Tennessee
United States	Cohen Children's Hospital	New Hyde Park	New York
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (Peds)	Portland	Oregon
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth University MCV Hospitals	Richmond	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Washington University/Barnes Jewish Hospital	Saint Louis	Missouri
United States	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri
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	Texas Transplant Institute	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Hospital and Clinics	Stanford	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (5)

Lead Sponsor	Collaborator
Medical College of Wisconsin	Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Marrow Donor Program

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (7)

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 — View Citation

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 Unre — View Citation

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. 201 — View Citation

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, Lo — View Citation

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 subg — View Citation

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 de — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two-year Overall Survival	Overall survival rate at 2 years according to an intention-to-treat analysis.	Measured at 2 years
Secondary	Neutrophil Engraftment		Measured at Day 28
Secondary	Platelet Engraftment		Measured at Day 180
Secondary	Graft Failure		Measured at 28 and 100 days
Secondary	Extensive Chronic Graft-versus-host Disease (GVHD)		Measured at 730 days
Secondary	Chronic GVHD		Measured at 2 years
Secondary	Relapse	Analysis restricted to patients who received the transplant.	Measured at 2 years
Secondary	Infections	Number of infection reports per patient.	Measured at 1 and 2 years
Secondary	Grades III-V Unexpected Adverse Events		Measured by 2 years
Secondary	Acute GVHD Grade II-IV		100 days, 180 days
Secondary	Acute GVHD Grade III-IV		100 days, 180 days
Secondary	Current Immunosuppressive (IS) Free Survival	This outcome measure takes into account subsequent immunosuppressive therapy that may occur following discontinuation of initial immunosuppressive therapy.	Measured at 2 years
Secondary	Immune Reconstitution		Measured at 100 days, 6 months, and 1 and 2 years
Secondary	Donor Recovery of Baseline Complete Blood Count (CBC) and White Blood Cell Count (WBC) Differential		Measured at 1, 6, and 12 months
Secondary	Donor Recovery to Baseline Toxicity Scores		Measured at 1, 6, and 12 months
Secondary	Donor Quality of Life		Measured at 1, 6, and 12 months
Secondary	Patient Quality of Life		Measured at baseline, 6 months, and 1, 2, and 5 years

External Links

•   Blood and Marrow Transplant Clinical Trials Network
•   National Marrow Donor Program