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Bone Marrow Transplant From Partially Matched Donors and Nonmyeloablative Conditioning for Blood Cancers (BMT CTN 0603)

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.
 
ClinicalTrials.gov Identifier: NCT00849147
Recruitment Status : Completed
First Posted : February 23, 2009
Results First Posted : September 7, 2015
Last Update Posted : December 22, 2017
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE February 20, 2009
First Posted Date  ICMJE February 23, 2009
Results First Submitted Date  ICMJE May 20, 2015
Results First Posted Date  ICMJE September 7, 2015
Last Update Posted Date December 22, 2017
Study Start Date  ICMJE October 2008
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2009)
Overall Survival at 180 Days From the Time of Transplant [ Time Frame: Measured at Month 6 and Year 1 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 20, 2009)
Overall Survival at 180 Days From the Time of Transplant [ Time Frame: Measured at 6 months and 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2016)
  • Neutrophil Recovery [ Time Frame: Measured at Days 28, 56, 90, and 100 ]
    Cumulative incidence of neutrophil recovery >500/μL at day +56
  • Primary Graft Failure [ Time Frame: Measured at Day 67 ]
    Primary graft failure is defined as < 5% donor chimerism on all measurements.
  • Secondary Graft Failure [ Time Frame: Measured at Day 100 ]
    Secondary graft failure is defined as initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and absolute neutrophil count is < 500/mm3, then it will be counted as a secondary graft failure.
  • Platelet Recovery [ Time Frame: Measured at Days 56, 90, and 100 ]
    Platelet Recovery to 20K
  • Platelet Recovery [ Time Frame: Measured at Days 56, 90, and 100 ]
    Platelet Recovery to 50K
  • 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.
  • Acute Graft-versus-host Disease (GVHD) [ Time Frame: Measured at Day 100 ]
  • Chronic GVHD [ Time Frame: Measured at Year 1 ]
  • Progression-free Survival [ Time Frame: Measured at Year 1 ]
    Progression-free survival is defined as the minimum time interval of the times to relapse/recurrence, to death or to last follow-up.
  • Treatment-related Mortality (TRM) [ Time Frame: Measured at 6 months and 1 year ]
  • Infections [ Time Frame: Measured at Year 1 ]
    Number of infections; infections will be reported by anatomic site, date of onset, organism and resolution, if any. Patients will be followed for infection for 1 year post-transplant.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2009)
  • Neutrophil Recovery [ Time Frame: Measured at Day 28 ]
  • Primary Graft Failure [ Time Frame: Measured at Day 56 ]
  • Secondary Graft Failure [ Time Frame: Measured at Day 100 ]
  • Platelet Recovery [ Time Frame: Measured at Days 100 and 180 ]
  • Donor cell engraftment [ Time Frame: Measured at Day 56 ]
  • Acute graft-versus-host disease [ Time Frame: Measured at Day 100 ]
  • Chronic graft-versus-host disease [ Time Frame: Measured at 1 year ]
  • Progression-free Survival [ Time Frame: Measured at 1 year ]
  • Treatment-related Mortality (TRM) [ Time Frame: Measured at Day 100 ]
  • Infections [ Time Frame: Measured at 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bone Marrow Transplant From Partially Matched Donors and Nonmyeloablative Conditioning for Blood Cancers (BMT CTN 0603)
Official Title  ICMJE 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)
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Burkitt Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
Intervention  ICMJE
  • 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.

  • Biological: GVHD prophylaxis

    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
Study Arms  ICMJE Experimental: Haploidentical Bone Marrow Transplant
Participants will receive a human leucocyte antigen (HLA) haploidentical bone marrow transplantation using a non-myeloablative preparative regimen, GVHD prophylaxis.
Interventions:
  • Biological: Haploidentical Bone Marrow Transplantation
  • Biological: GVHD prophylaxis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2010)
55
Original Estimated Enrollment  ICMJE
 (submitted: February 20, 2009)
50
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00849147
Other Study ID Numbers  ICMJE BMTCTN0603
U01HL069294 ( U.S. NIH Grant/Contract )
5U24CA076518 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Results will be published in a manuscript
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public.
URL: https://biolincc.nhlbi.nih.gov/home/
Responsible Party Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Blood and Marrow Transplant Clinical Trials Network
  • National Cancer Institute (NCI)
  • National Marrow Donor Program
Investigators  ICMJE
Study Director: Mary Horowitz, MD, MS Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP