Bone Marrow Transplant From Partially Matched Donors and Nonmyeloablative Conditioning for Blood Cancers (BMT CTN 0603)
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
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Haploidentical Bone Marrow Transplantation; GVHD prophylaxis
Intervention type(s): Biological; Biological
Intervention description(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Lymphoblastic Leukemia/Lymphoma; Acute Myelogenous Leukemia; Mantel-Cell Lymphoma; Hematopoietic Transplant; Haplo-Identical Transplant; Non-Myeloablative Transplant