Intensity-Modulated Radiation Therapy, Etoposide, and Cyclophosphamide Followed By Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

OBJECTIVES: I. To establish the maximum tolerated dose [MTD] of large field image-guided
IMRT, using helical tomotherapy when given in combination with intravenous cyclophosphamide
and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation
(HSCT) from an human leukocyte antigen (HLA)-identical sibling or unrelated donor in patients
with ALL or AML with induction failure or in relapse. (Phase I) II. To describe the toxicity
at each dose level standard. (Phase I) III. To collect data on the radiation dose to normal
organs and bone marrow using tomotherapy targeted total-body irradiation (TBI). (Phase I) IV.
To estimate the overall survival probability, disease free survival probability and relapse
rate associated with this regimen. (Phase II) V. To characterize the treatment related
mortality and toxicity profile (early/late) associated with this regimen. (Phase II) VI. To
descriptively compare the outcomes of patients treated on this protocol to a comparable
patient population conditioned with whole body radiation. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy
(IMRT) followed by a phase II study.

PREPARATIVE REGIMEN: Patients undergo IMRT using helical tomotherapy once or twice daily on
days -10 to -6 or -10 to -7. Patients also receive etoposide intravenously (IV) on day -6 or
-5 and cyclophosphamide IV on day -4 or -3.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell or bone marrow
transplantation on day -1 or day 0. After completion of study treatment, patients are
followed up periodically for up to 2 years.

Inclusion Criteria:

- Patients with acute lymphocytic leukemia or acute myelogenous leukemia who are not in
first or second remission (i.e., after failing remission induction therapy or in
relapse or beyond second remission)

- All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR)
identical sibling who is willing to donate bone marrow or primed blood stem cells or a
10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR, or DQ
and a KIR mismatch at C will be allowed; all ABO blood group combinations of the
donor/recipient are acceptable since even major ABO compatibilities can be dealt with
by various techniques

- Prior therapy with VP-16, Busulfan, and Cytoxan is allowed

- A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal
rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan
(MUGA) or echocardiogram

- Patients must have a serum creatinine of less than or equal to 1.2 or creatinine
clearance > 80 ml/min

- A bilirubin of less than or equal to 1.5

- Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of
normal

- Serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of
normal

- Pulmonary functioning tests including diffusing capacity of carbon monoxide (DLCO)
will be performed; forced expiratory volume in one second (FEV1) and DLCO should be
greater than 50% of the predicted normal value

- The time from the end last induction or reinduction attempt should be >= 14 days

- Signed informed consent form approved by the Institutional Review Board (IRB) is
required

DONOR: Any sibling donors who are histocompatible with the prospective recipient will be
considered a suitable donor

- Donors will be excluded if for psychological or medical reasons they are unable to
tolerate the procedure

- Donor should be able to donate peripheral blood stem cells or bone marrow

Exclusion Criteria:

- Prior radiation therapy that would exclude the use of total-body irradiation

- Patients who have undergone bone marrow transplantation previously and who have
relapsed

- Patients with psychological or medical condition that patients physician deems
unacceptable to proceed to allogeneic bone marrow transplant

- Pregnancy

- Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an
echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction < 50%