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

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.

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