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

This study has been completed.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00075816
First received: January 9, 2004
Last updated: March 21, 2016
Last verified: March 2016
  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
Leukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Biological: Allogeneic bone marrow transplantation
Biological: Peripheral blood stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Two-year Overall Survival [ Time Frame: Measured at 2 years ] [ Designated as safety issue: No ]
    Overall survival rate at 2 years according to an intention-to-treat analysis.


Secondary Outcome Measures:
  • Neutrophil Engraftment [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: No ]
  • Platelet Engraftment [ Time Frame: Measured at Day 180 ] [ Designated as safety issue: No ]
  • Graft Failure [ Time Frame: Measured at 28 and 100 days ] [ Designated as safety issue: Yes ]
  • Extensive Chronic Graft-versus-host Disease (GVHD) [ Time Frame: Measured at 730 days ] [ Designated as safety issue: No ]
  • Chronic GVHD [ Time Frame: Measured at 2 years ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: Measured at 2 years ] [ Designated as safety issue: No ]
    Analysis restricted to patients who received the transplant.

  • Infections [ Time Frame: Measured at 1 and 2 years ] [ Designated as safety issue: No ]
    Number of infection reports per patient.

  • Grades III-V Unexpected Adverse Events [ Time Frame: Measured by 2 years ] [ Designated as safety issue: Yes ]
  • Acute GVHD Grade II-IV [ Time Frame: 100 days, 180 days ] [ Designated as safety issue: No ]
  • Acute GVHD Grade III-IV [ Time Frame: 100 days, 180 days ] [ Designated as safety issue: No ]
  • Current Immunosuppressive (IS) Free Survival [ Time Frame: Measured at 2 years ] [ Designated as safety issue: No ]
    This outcome measure takes into account subsequent immunosuppressive therapy that may occur following discontinuation of initial immunosuppressive therapy.

  • Immune Reconstitution [ Time Frame: Measured at 100 days, 6 months, and 1 and 2 years ] [ Designated as safety issue: No ]
  • Donor Recovery of Baseline Complete Blood Count (CBC) and White Blood Cell Count (WBC) Differential [ 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 Quality of Life [ Time Frame: Measured at 1, 6, and 12 months ] [ 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 ]

Enrollment: 551
Study Start Date: January 2004
Study Completion Date: April 2014
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bone Marrow Transplant
Allogeneic bone marrow transplantation
Biological: Allogeneic bone marrow transplantation
Bone marrow transplant from HLA compatible unrelated donors.
Active Comparator: Blood Stem Cell Transplant
Peripheral blood stem cell transplantation
Biological: Peripheral blood stem cell transplantation
Peripheral blood transplant from HLA compatible unrelated donors.

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.

  Eligibility

Ages Eligible for Study:   up to 66 Years   (Child, Adult, Senior)
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 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 45 Study Locations
Sponsors and Collaborators
Medical College of Wisconsin
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Investigators
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
  More Information

Additional Information:
Publications:
Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00075816     History of Changes
Obsolete Identifiers: NCT00321776, NCT00473395
Other Study ID Numbers: BMTCTN0201  U01HL069294-05  BMT CTN 0201  5U24CA076518 
Study First Received: January 9, 2004
Results First Received: January 22, 2015
Last Updated: March 21, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript.

Additional relevant MeSH terms:
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on July 26, 2016