Evaluating the Safety and Effectiveness of a Bone Marrow Transplant From Partially Matched Donors and Using Low Dose Chemotherapy in People With Leukemia or Lymphoma (BMT CTN #0603)

This study has been completed.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00849147
First received: February 20, 2009
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

Bone marrow transplants are one treatment option for people with leukemia or lymphoma. Family members or unrelated donors with a similar type of bone marrow usually donate their bone marrow to the transplant patients. This study will evaluate the effectiveness of a new type of bone marrow transplant—one that uses lower doses of chemotherapy and bone marrow donated from family members with only partially matched bone marrow—in people with leukemia or lymphoma.


Condition Intervention Phase
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Burkitt Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Biological: Haploidentical Bone Marrow Transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Overall survival at 180 days from the time of transplant [ Time Frame: Measured at Month 6 and Year 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neutrophil recovery [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: No ]
  • Primary graft failure [ Time Frame: Measured at Day 56 ] [ Designated as safety issue: Yes ]
  • Secondary graft failure [ Time Frame: Measured at Day 100 ] [ Designated as safety issue: Yes ]
  • Platelet recovery [ Time Frame: Measured at Days 100 and 180 ] [ Designated as safety issue: No ]
  • Donor cell engraftment [ Time Frame: Measured at Day 56 ] [ Designated as safety issue: No ]
  • Acute graft-versus-host disease (GVHD) [ Time Frame: Measured at Day 100 ] [ Designated as safety issue: No ]
  • Chronic GVHD [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
  • Treatment-related mortality (TRM) [ Time Frame: Measured at Day 100 ] [ Designated as safety issue: Yes ]
  • Infections [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: October 2008
Study Completion Date: November 2013
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive a human leucocyte antigen (HLA)-haploidentical bone marrow transplant using a non-myeloablative preparative regimen.
Biological: Haploidentical Bone Marrow Transplantation

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

  • Fludarabine: 30 mg/m2 intravenously (IV) on Days -6, -5, -4, -3, and -2
  • Cyclophosphamide (Cy): 14.5 mg/kg IV on Days -6 and -5
  • Total body irradiation (TBI): 200 centigray (cGy) on Day -1

Day 0 is the day of the infusion of non-T-cell depleted bone marrow. The bone marrow will be obtained from haploidentical related donor.

The GVHD prophylaxis regimen will consist of the following:

  • Cy: 50 mg/kg IV on Days 3 and 4
  • Tacrolimus: (IV or orally) beginning on Day 5 with dose adjusted to maintain a level of 5 to 15 mg/mL
  • Mycophenolate mofetil (MMF): 15 mg/kg orally three times a day (TID) beginning on Day 5; maximum dose will be 1 g orally TID
  • Granulocyte-colony stimulating factor (G-CSF) 5 mcg/kg/day beginning on Day 5 until absolute neutrophil count (ANC) is greater than or equal to 1,000/mm^3 for 3 consecutive days

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, 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 lymphoma.

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' lives.

  Eligibility

Ages Eligible for Study:   1 Year to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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
  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: NCT00849147

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
University of California San Diego Medical Center
La Jolla, California, United States, 92093
United States, Florida
University of Florida College of Medicine (Shands)
Gainesville, Florida, United States, 32610-0277
United States, Georgia
Bone Marrow Transplant Group of Georgia, Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Hawaii
Kapi'olani Medical Center for Women and Children, University of Hawaii
Honolulu, Hawaii, United States, 96826
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center (SKCCC)
Baltimore, Maryland, United States, 21231
University of Maryland, Greenbaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
DFCI, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Karmanos Cancer Institute, Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University, Barnes Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Fox Chase, Temple University
Philadelphia, Pennsylvania, United States, 19111-2442
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-8210
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Director: Mary Horowitz, MD, MS Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
  More Information

Additional Information:
No publications provided by Medical College of Wisconsin

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00849147     History of Changes
Other Study ID Numbers: 605, U01HL069294
Study First Received: February 20, 2009
Last Updated: November 22, 2013
Health Authority: United States: Federal Government

Keywords provided by Medical College of Wisconsin:
Acute Lymphoblastic Leukemia/Lymphoma
Acute Myelogenous Leukemia
Mantel-Cell Lymphoma
Hematopoietic Transplant
Haplo-Identical Transplant
Non-Myeloablative Transplant

Additional relevant MeSH terms:
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
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014