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

Phase 2

Completed

Conditions: Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Lymphoma, B-Cell
Burkitt Lymphoma

Interventions: Biological: Haploidentical Bone Marrow Transplantation
Biological: GVHD prophylaxis

Registration Number: NCT00849147

Lead Sponsor: Medical College of Wisconsin

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Haploidentical Bone Marrow Transplant	Haploidentical Bone Marrow Transplantation	Participants will receive a human leucocyte antigen (HLA) haploidentical bone marrow transplantation using a non-myeloablative preparative regimen, GVHD prophylaxis.
Haploidentical Bone Marrow Transplant	GVHD prophylaxis	Participants will receive a human leucocyte antigen (HLA) haploidentical bone marrow transplantation using a non-myeloablative preparative regimen, GVHD prophylaxis.

Primary Outcome Measures

Name	Time	Method
Overall Survival at 180 Days From the Time of Transplant	Measured at Month 6 and Year 1

Secondary Outcome Measures

Name	Time	Method
Acute Graft-versus-host Disease (GVHD)	Measured at Day 100
Treatment-related Mortality (TRM)	Measured at 6 months and 1 year
Secondary Graft Failure	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.
Neutrophil Recovery	Measured at Days 28, 56, 90, and 100	Cumulative incidence of neutrophil recovery \>500/μL at day +56
Primary Graft Failure	Measured at Day 67	Primary graft failure is defined as \< 5% donor chimerism on all measurements.
Platelet Recovery	Measured at Days 56, 90, and 100	Platelet Recovery to 50K
Chronic GVHD	Measured at Year 1
Donor Cell Engraftment	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.
Infections	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.
Progression-free Survival	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.

Trial Locations

Locations (17): City of Hope National Medical Center
🇺🇸
Duarte, California, United States
University of California San Diego Medical Center
🇺🇸
La Jolla, California, United States
Washington University, Barnes Jewish Hospital
🇺🇸
Saint Louis, Missouri, United States
University of Florida College of Medicine (Shands)
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Gainesville, Florida, United States
Bone Marrow Transplant Group of Georgia, Northside Hospital
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Atlanta, Georgia, United States
Kapi'olani Medical Center for Women and Children, University of Hawaii
🇺🇸
Honolulu, Hawaii, United States
University of Maryland, Greenbaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center (SKCCC)
🇺🇸
Baltimore, Maryland, United States
DFCI, Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Karmanos Cancer Institute, Children's Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Fox Chase, Temple University
🇺🇸
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Texas Transplant Institute
🇺🇸
San Antonio, Texas, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States