Clinical trial NCT00849147: Bone Marrow Transplant From Partially Matched Donors and Nonmyeloablative Conditioning for Blood Cancers (BMT CTN 0603)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Burkitt Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Keywords: Acute Lymphoblastic Leukemia/Lymphoma
Acute Myelogenous Leukemia
Mantel-Cell Lymphoma
Hematopoietic Transplant
Haplo-Identical Transplant
Non-Myeloablative Transplant
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Blood and Marrow Transplant Clinical Trials Network
name: National Cancer Institute (NCI)
name: National Marrow Donor Program
First posted: 2009-02-23
Enrollment: 55
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival at 180 Days From the Time of Transplant
timeFrame: Measured at Month 6 and Year 1
Secondary outcomes:
measure: Neutrophil Recovery
timeFrame: Measured at Days 28, 56, 90, and 100
measure: Primary Graft Failure
timeFrame: Measured at Day 67
measure: Secondary Graft Failure
timeFrame: Measured at Day 100
measure: Platelet Recovery
timeFrame: Measured at Days 56, 90, and 100
measure: Platelet Recovery
timeFrame: Measured at Days 56, 90, and 100
measure: Donor Cell Engraftment
timeFrame: Measured at Day 56
measure: Acute Graft-versus-host Disease (GVHD)
timeFrame: Measured at Day 100
measure: Chronic GVHD
timeFrame: Measured at Year 1
measure: Progression-free Survival
timeFrame: Measured at Year 1
measure: Treatment-related Mortality (TRM)
timeFrame: Measured at 6 months and 1 year
measure: Infections
timeFrame: Measured at Year 1
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine (Shands)
state: Florida
city: Atlanta
country: United States
facility: Bone Marrow Transplant Group of Georgia, Northside Hospital
state: Georgia
city: Honolulu
country: United States
facility: Kapi'olani Medical Center for Women and Children, University of Hawaii
state: Hawaii
city: Baltimore
country: United States
facility: University of Maryland, Greenbaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center (SKCCC)
state: Maryland
city: Boston
country: United States
facility: DFCI, Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute, Children's Hospital of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University, Barnes Jewish Hospital
state: Missouri
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase, Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
name: Mary Horowitz, MD, MS
role: STUDY_DIRECTOR
References:
citation: Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; Blood and Marrow Transplant Clinical Trials Network. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. doi: 10.1182/blood-2011-03-344853. Epub 2011 Apr 28.
citation: Eapen M, O'Donnell P, Brunstein CG, Wu J, Barowski K, Mendizabal A, Fuchs EJ. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Oct;20(10):1485-92. doi: 10.1016/j.bbmt.2014.05.015. Epub 2014 May 23.