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A Multi-Center, Phase II Trial of Nonmyeloablative Conditioning (NST) and Transplantation of Partially HLA-Mismatched Bone Marrow From Related Donors for Patients With Hematologic Malignancies (BMT CTN #0603)

Phase 2
1 Year
70 Years
Open (Enrolling)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Burkitt Lymphoma, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse

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Trial Information

A Multi-Center, Phase II Trial of Nonmyeloablative Conditioning (NST) and Transplantation of Partially HLA-Mismatched Bone Marrow From Related Donors for Patients With Hematologic Malignancies (BMT CTN #0603)

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, a bone marrow transplant is another treatment
option. In a bone marrow transplant procedure, healthy bone marrow is taken from a donor and
transplanted into the patient. Bone marrow can be donated by a family member or an unrelated
donor who has a similar type of bone marrow. Most bone marrow transplants are performed
using a donor who is a perfect or close-to-perfect tissue match. However, for participants
in this study, researchers have determined that a completely matched donor is unavailable
within participants' families, and an unrelated donor match has not been found either.
Participants do, however, have a family member who is a partial tissue match. Typically,
people who are undergoing a bone marrow transplant receive high doses of chemotherapy before
the transplant to prepare their bodies to accept the donor bone marrow. In this study,
participants will undergo a new type of bone marrow 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 bone marrow transplant that uses partially matched bone
marrow donated by a family member as a treatment option for people with leukemia or

This study will enroll people with leukemia or lymphoma who have a family member with a
partial tissue match. Participants will be admitted to the hospital and will first receive a
type of chemotherapy called fludarabine, which will be given intravenously for 5 days. In
addition, another type of chemotherapy, cyclophosphamide, will be given intravenously on the
first and second day. After 5 days, participants will receive a small dose of radiation. The
next day, participants will undergo the bone marrow transplant. The third and fourth day
after the transplant, participants will receive high doses of cyclophosphamide to help
prevent two complications, graft rejection, which occurs when the body's immune system
rejects the donor bone marrow, and graft-versus-host disease (GVHD), which is an attack by
the donor cells on the body's normal tissues. On the fifth day after the transplant,
participants will receive two additional medications, tacrolimus and mycophenolate mofetil
(MMF), to help prevent GVHD; some participants may receive cyclosporine instead of
tacrolimus. Participants will receive MMF for about 5 weeks and tacrolimus for about 6
months. Also beginning on the fifth 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 remain in the hospital for approximately 2 to 3 months, but possibly
longer if there are complications. 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. Follow-up study visits will occur 6 months and 1 year after the transplant. At
Months 1, 2, 6, and 12 after the transplant, blood or bone marrow 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'

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)

- Donor must be at least 18 years of age

- Human leucocyte antigen (HLA) typing will be performed at high resolution (allele
level) for the HLA-A, -B, Cw, DRB1, and -DQB1 loci. A minimum match of 5/10 is
required. An 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. The donor and recipient must be identical, as
determined by high resolution typing, on at least one allele of each of the following
genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. Fulfillment of this
criterion shall be considered sufficient evidence that the donor and recipient share
one HLA haplotype, and typing of additional family members is not required.

- 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:

1. Heart: left ventricular ejection fraction at rest must be greater than or equal
to 35%, or shortening fraction greater than 25%

2. Liver: bilirubin less than or equal to 2.5 mg/dL and alanine aminotransferase
(ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than five
times the upper limit of normal

3. 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]) is greater than 40 mL/min/1.73m^2

4. Pulmonary: 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.

5. Performance status: Karnofsky/Lansky score greater than or equal to 60%

Exclusion Criteria:

- Have an HLA-matched, related, or 7 or 8/8 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival at 180 days from the time of transplant

Outcome Time Frame:

Measured at Month 6 and Year 1

Safety Issue:


Principal Investigator

Mary Horowitz, MD, MS

Investigator Role:

Study Director

Investigator Affiliation:

Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin


United States: Federal Government

Study ID:




Start Date:

October 2008

Completion Date:

September 2013

Related Keywords:

  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Burkitt Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Acute Lymphoblastic Leukemia/Lymphoma
  • Acute Myelogenous Leukemia
  • Mantel-Cell Lymphoma
  • Hematopoietic Transplant
  • Haplo-Identical Transplant
  • Non-Myeloablative Transplant
  • Burkitt Lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse



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City of Hope National Medical CenterLos Angeles, California  91010
Baylor University Medical CenterDallas, Texas  75246
Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
Oregon Health & Science UniversityPortland, Oregon  97201
Texas Transplant InstituteSan Antonio, Texas  78229
University of Florida College of Medicine (Shands)Gainesville, Florida  32610
University of Maryland, Greenbaum Cancer CenterBaltimore, Maryland  21201
University of California San Diego Medical CenterSan Diego, California  92103-8409
Bone Marrow Transplant Group of Georgia, Northside HospitalAtlanta, Georgia  30342
Kapi'olani Medical Center for Women and Children, University of HawaiiHonolulu, Hawaii  96826
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center (SKCCC)Baltimore, Maryland  21231
DFCI, Massachusetts General HospitalBoston, Massachusetts  02114
Karmanos Cancer Institute, Children's Hospital of MichiganDetroit, Michigan  48201
Washington University, Barnes Jewish HospitalSt. Louis, Missouri  63110
Fox Chase, Temple UniversityPhiladelphia, Pennsylvania  19111-2442