Working… Menu

Evaluating the Safety and Effectiveness of an Umbilical Cord Blood Stem Cell Transplant (BMT CTN 0604)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00864227
Recruitment Status : Completed
First Posted : March 18, 2009
Results First Posted : August 28, 2015
Last Update Posted : October 27, 2017
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:
A bone marrow transplant, which is a type of stem cell transplant, is a treatment option for people with leukemia or lymphoma. Recently, stem cell transplants using umbilical cord blood have become a treatment option for people with these types of cancers. This study will evaluate the effectiveness of a stem cell transplant using umbilical cord blood, along with lower doses of chemotherapy, to treat people with leukemia or lymphoma.

Condition or disease Intervention/treatment Phase
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Burkitt Lymphoma Lymphoma, B-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Biological: Hematopoietic Umbilical Cord Blood Stem Cell Transplantation Biological: GVHD prophylaxis Phase 2

Detailed Description:

Leukemia and lymphoma are types of blood cancers. Chemotherapy is a common treatment option for people with these types of cancers, but if the cancer does not respond well to chemotherapy, or if the cancer returns, people may need to consider other options. A bone marrow transplant, which is a type of stem cell transplant in which healthy bone marrow is donated to a patient by a related or unrelated donor, is commonly used to treat leukemia and lymphoma. Recently, stem cell transplants using umbilical cord blood have become a viable option to treat these types of cancers. Traditionally, umbilical cord blood, which is the blood left over in the placenta after a baby is born, has been disposed of with the placenta. However, over the past few years, doctors have begun to collect and freeze the umbilical cord blood cells so that they may be used in stem cell transplant procedures at a later time.

Typically, people who are undergoing a stem cell transplant receive high doses of chemotherapy before the transplant to prepare their bodies to accept the donor stem cells. In this study, participants will undergo a new type of stem cell transplant called a nonmyeloablative transplant, which is a reduced intensity method of transplantation that does not require high doses of chemotherapy. The purpose of the study is to examine the safety and effectiveness of a nonmyeloablative stem cell transplant that uses umbilical cord blood as a treatment option for people with leukemia or lymphoma.

This study will enroll people with leukemia or lymphoma. Participants will be admitted to the hospital and will first receive a type of chemotherapy called cyclophosphamide, which will be given intravenously on the sixth day before the transplant. In addition, another type of chemotherapy, fludarabine, will be given intravenously each day for 5 days before the transplant. Three days before the transplant, participants will receive cyclosporine and mycophenolate mofetil (MMF), to help prevent the body from rejecting the stem cells and to help decrease the risk of developing a complication called graft-versus-host-disease (GVHD), which is an attack by the donor cells on the body's normal tissues. Some participants may receive tacrolimus instead of cyclosporine. After 6 days, participants will receive a small dose of radiation. The next day, participants will undergo the umbilical cord blood stem cell transplant.

Participants will remain in the hospital for approximately 2 to 3 months total, but possibly longer if there are complications. Beginning on the first day after the transplant, participants will receive daily injections of a growth factor called granulocyte-colony stimulating factor (G-CSF), which is a natural protein that increases the white blood cell count; G-CSF will be continued until a participant's white blood cell count is normal again. Participants will continue to receive MMF for 30 days and cyclosporine or tacrolimus for 180 days after the transplant. While participants are in the hospital, blood samples will be collected regularly to evaluate the response and possible side effects to treatment, including GVHD. If necessary, participants will receive platelet and red blood cell transfusions. At follow-up study visits 6 months and 1 year after the transplant, blood samples will be obtained. Study researchers will keep track of participants' medical condition through phone calls or mailings to participants and their doctors once a year for the rest of the participants' lives.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Phase II Trial of Non-Myeloablative Conditioning (NST) and Transplantation of Umbilical Cord Blood (UCB) From Unrelated Donors in Patients With Hematologic Malignancies (BMT CTN #0604)
Study Start Date : December 2008
Actual Primary Completion Date : April 2011
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: Umbilical Cord Blood Transplantation
Participants will receive a double unit Hematopoietic Umbilical Cord Blood Stem Cell Transplantation using a non-myeloablative preparative regimen, GVHD prophylaxis.
Biological: Hematopoietic Umbilical Cord Blood Stem Cell Transplantation

The transplant preparative regimen is listed below. The - sign is the number of days before the transplant.

  • Fludarabine: 40 mg/m^2 intravenously (IV) on Days -6, -5, -4, -3, and -2
  • Cyclophosphamide: 50 mg/kg IV on Day -6
  • Total body irradiation: 200 centigray (cGy) on Day -1

Biological: GVHD prophylaxis

GVHD prophylaxis regimen will consist of:

  • Cyclosporine: beginning on Day -3 with the dose adjusted to maintain a level of 200-400 mg/mL
  • MMF: 1 gram IV three times a day (TID) if greater than 50 kg, or 15 mg/kg IV TID if less than 50 kg beginning on Day -3; continued until Day 30 or 7 days after engraftment, whichever day is later

Day 0 is the day of the infusion of the umbilical cord blood graft units, which will be obtained from partially HLA-matched unrelated donors.

Beginning on Day 1, participants will receive G-CSF 5 mcg/kg/day until absolute neutrophil count (ANC) is greater than or equal to 2,000/mm^3 for three consecutive measurements, each on different days.

Primary Outcome Measures :
  1. Overall Survival at 180 Days From the Time of Transplant [ Time Frame: Measured at Month 6 and Year 1 ]

Secondary Outcome Measures :
  1. Neutrophil Recovery [ Time Frame: Measured at Days 28, 56, 90, and 100 ]
    Neutrophil recovery is defined as achieving an absolute neutrophil count ≥ 500/mm3 for three consecutive measurements on different days.

  2. Primary Graft Failure [ Time Frame: Measured at Day 100 ]
    Primary graft failure is defined as < 5% donor chimerism on all measurements prior to and day-100.

  3. Secondary Graft Failure [ Time Frame: Measured at Day 100 ]
    Secondary graft failure is defined initial recovery followed by neutropenia with < 5% donor chimerism.

  4. Platelet Recovery to 20K [ Time Frame: Measured at Days 56, 90, and 100 ]
    Platelet recovery is defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count >20,000/mm3 with no platelet transfusions in the preceding seven days.

  5. Donor Cell Engraftment [ Time Frame: Measured at Day 56 ]
    Marrow or Blood Sample. Donor cell engraftment is defined as donor chimerism ≥ 5% on Day ≥ 56 after transplantation. Chimerism should be evaluated on Days ~28, ~56, ~180, and ~365 after transplantation. Chimerism may be evaluated in whole blood or mononuclear fraction.

  6. Acute Graft-versus-host Disease (GVHD) [ Time Frame: Measured at Day 100 ]
  7. Chronic GVHD [ Time Frame: Measured at Year 1 ]
  8. Progression-free Survival [ Time Frame: Measured at Year 1 ]
    Progression-free survival is defined as the minimum time interval to relapse/ recurrence/progression, to death or to last follow-up.

  9. Treatment-related Mortality (TRM) [ Time Frame: Measured at 6 months and 1 year ]
  10. Incidence of Infections [ Time Frame: Measured at Year 1 ]
    Number of participants that experienced at least one infection.

  11. Platelet Recovery to 50K [ Time Frame: Measured at Days 56, 90, and 100 ]
    Platelet recovery is defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count >50,000/mm3 with no platelet transfusions in the preceding seven days.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   1 Year to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants must be 21 to 70 years old; participants 1 to 21 years old are also eligible if they are ineligible for BMT CTN #0501 (NCT00412360)
  • Each unit must supply a minimum of 1.5 x 10^7/kg pre-cryopreserved nucleated cell dose
  • Participants must have two partially human leucocyte antigen (HLA)-matched umbilical cord blood units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0 to 2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. Each unit must be a 4 to 6 HLA-A, B, and DRB1 antigen matched to each other, not necessarily at the same loci as with the recipient. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1 for this study. An adult unrelated donor search is not required for a person to be eligible for this study if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6 to 8 weeks from referral to transplant center or low likelihood of finding a matched, unrelated donor.
  • Must have received cytotoxic chemotherapy within 3 months of the consent date (measured from the start date of chemotherapy)
  • Acute leukemias (includes T lymphoblastic lymphoma) in the second or subsequent complete remission (CR)
  • Burkitt's lymphoma in the second or subsequent CR
  • Lymphoma
  • Patients with adequate physical function, as measured by the following:

    • Heart: left ventricular ejection fraction at rest greater than 35%, or shortening fraction greater than 25%
    • Liver: bilirubin less than or equal to 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than or equal to five times the upper limit of normal
    • Kidney: serum creatinine within normal range for age, or if serum creatinine is outside the normal range for age, then kidney function (creatinine clearance or glomerular filtration rate (GFR) greater than 40 mL/min/1.73m^2
    • Lungs: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) greater than 50% predicted (corrected for hemoglobin). If unable to perform pulmonary function tests, then oxygen (O2) saturation must be greater than 92% on room air.

Exclusion Criteria:

  • Have an HLA-matched, related, or 7 or 8/8 HLA allele matched (HLA-A, -B, -Cw, -DRB1) related donor able to donate
  • Had an autologous hematopoietic stem cell transplant in the 3 months before study entry
  • Pregnant or breastfeeding
  • Evidence of HIV infection or known HIV positive serology
  • Current uncontrolled bacterial, viral, or fungal infection (i.e., currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
  • Prior allogeneic hematopoietic stem cell transplant
  • History of primary idiopathic myelofibrosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00864227

Layout table for location information
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Florida
University of Florida College of Medicine, Shands
Gainesville, Florida, United States, 32610-3633
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33624
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242-1009
United States, Kansas
University of Kansas Hospital
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Dana-Farber Cancer Institute (DFCI), Brigham & Women's Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute (DFCI), Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University, Barnes Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, New York
Weill Cornell Medical College, NY Presbyterian Hospital
New York, New York, United States, 10065
United States, Ohio
Ohio State, Arthur G. James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University, Medical College of Virginia (MCV) Hospital
Richmond, Virginia, United States, 23298
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792-5156
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)
National Marrow Donor Program
Layout table for investigator information
Study Director: Mary Horowitz, MD, MS Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: Medical College of Wisconsin Identifier: NCT00864227    
Other Study ID Numbers: BMTCTN0604
U01HL069294 ( U.S. NIH Grant/Contract )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Posted: March 18, 2009    Key Record Dates
Results First Posted: August 28, 2015
Last Update Posted: October 27, 2017
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public
Keywords provided by Medical College of Wisconsin:
Acute Lymphoblastic Leukemia/Lymphoma
Acute Myelogenous Leukemia
Mantel-Cell Lymphoma
Hematopoietic Transplant
Umbilical Cord Blood (UCB)
Non-Myeloablative Transplant
Additional relevant MeSH terms:
Layout table for MeSH terms
Burkitt Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin