Evaluating the Safety and Effectiveness of an Umbilical Cord Blood Stem Cell Transplant (BMT CTN 0604)
Condition: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Burkitt Lymphoma; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse
MeSH terms: Burkitt Lymphoma; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, B-Cell; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Hematopoietic Umbilical Cord Blood Stem Cell Transplantation; GVHD prophylaxis
Intervention description: The transplant preparative regimen is listed below. The - sign is the number of days before the transplant.
Fludarabine: 40 mg/m^2 intravenously (IV) on Days -6, -5, -4, -3, and -2
Cyclophosphamide: 50 mg/kg IV on Day -6
Total body irradiation: 200 centigray (cGy) on Day -1; GVHD prophylaxis regimen will consist of:
Cyclosporine: beginning on Day -3 with the dose adjusted to maintain a level of 200-400 mg/mL
MMF: 1 gram IV three times a day (TID) if greater than 50 kg, or 15 mg/kg IV TID if less than 50 kg beginning on Day -3; continued until Day 30 or 7 days after engraftment, whichever day is later
Day 0 is the day of the infusion of the umbilical cord blood graft units, which will be obtained from partially HLA-matched unrelated donors.
Beginning on Day 1, participants will receive G-CSF 5 mcg/kg/day until absolute neutrophil count (ANC) is greater than or equal to 2,000/mm^3 for three consecutive measurements, each on different days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 1 Year
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Acute Lymphoblastic Leukemia/Lymphoma; Acute Myelogenous Leukemia; Mantel-Cell Lymphoma; Hematopoietic Transplant; Umbilical Cord Blood (UCB); Non-Myeloablative Transplant

Summary:

      A bone marrow transplant, which is a type of stem cell transplant, is a treatment option for
      people with leukemia or lymphoma. Recently, stem cell transplants using umbilical cord blood
      have become a treatment option for people with these types of cancers. This study will
      evaluate the effectiveness of a stem cell transplant using umbilical cord blood, along with
      lower doses of chemotherapy, to treat people with leukemia or lymphoma.
    

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)

          -  Each unit must supply a minimum of 1.5 x 10^7/kg pre-cryopreserved nucleated cell dose

          -  Participants must have two partially human leucocyte antigen (HLA)-matched umbilical
             cord blood units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci
             with the recipient. This may include 0 to 2 antigen mismatches at each A or B (at the
             antigen level) or DRB1 (at the allele level) loci. Each unit must be a 4 to 6 HLA-A,
             B, and DRB1 antigen matched to each other, not necessarily at the same loci as with
             the recipient. All typing will be done using molecular typing. Though molecular level
             typing will be available, a match is defined at intermediate resolution for HLA-A and
             -B and at high resolution for -DRB1 for this study. An adult 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.

          -  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:

               -  Heart: left ventricular ejection fraction at rest greater than 35%, or shortening
                  fraction greater than 25%

               -  Liver: bilirubin less than or equal to 2.5 mg/dL and alanine aminotransferase
                  (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than or
                  equal to five times the upper limit of normal

               -  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) greater than 40 mL/min/1.73m^2

               -  Lungs: 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.

        Exclusion Criteria:

          -  Have an HLA-matched, related, or 7 or 8/8 HLA 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