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

• Maximum tolerated dose of intensity-modulated radiotherapy (Phase I) [ Time Frame: 30 days post transplant ] [ Designated as safety issue: Yes ]
• Toxicity as assessed by NCI CTCAE v3.0 (Phase I) [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
• Overall survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
• Relapse-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
• Event-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
• Treatment-related mortality (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
• Relative risk (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]

• Maximum tolerated dose of intensity-modulated radiotherapy (Phase I)
• Toxicity (Phase I)
• Overall survival (Phase II)
• Relapse-free survival (Phase II)
• Event-free survival (Phase II)
• Treatment-related mortality (Phase II)
• Relative risk (Phase II)

• Infection (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
• Acute and chronic graft-versus-host disease (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]

• Infection (Phase II)
• Acute and chronic graft-versus-host disease (Phase II)

RATIONALE: Giving intensity-modulated radiation therapy and chemotherapy, such as etoposide and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving intensity-modulated radiation therapy together with chemotherapy before transplant may stop this from happening.

PURPOSE: This phase I/II clinical trial is studying the side effects and best dose of intensity-modulated radiation therapy (IMRT) when given together with etoposide and cyclophosphamide followed by donor stem cell transplant and to see how well they work in treating patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia (AML).

OBJECTIVES:

• To establish the maximum tolerated dose of large field image-guided intensity-modulated radiotherapy using helical tomotherapy when given in combination with etoposide and cyclophosphamide as a preparative regimen followed by HLA-matched allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory acute lymphoblastic leukemia or acute myelogenous leukemia. (Phase I)
• To describe the toxicity at each dose level. (Phase I)
• To collect data on the radiation dose to normal organs and bone marrow using tomotherapy targeted total-body irradiation. (Phase I)
• To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this regimen. (Phase II)
• To characterize the treatment-related mortality and toxicity profile (early/late) associated with this regimen. (Phase II)
• To descriptively compare the outcomes of patients treated on this study to a comparable patient population conditioned with whole-body radiotherapy. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiotherapy (IMRT) using helical tomotherapy, followed by a phase II study. Patients are stratified by age (≥ 18 years of age but ≤ 55 years of age vs 6-17 years of age).

• 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.

• Drug: cyclophosphamide
  100 mg/kg (ideal body weight)on day -3 from transplant or day -4 when IMRT is given over 4 days.
• Drug: etoposide
  60 mg/kg (calculated on adjusted ideal body weight) on day -5 from transplant or day -6 when IMRT is given over 4 days.
• Procedure: allogeneic bone marrow transplantation
  Occurs approximately 48 hours after completion of cyclophosphamide
• Procedure: allogeneic hematopoietic stem cell transplantation
  Occurs approximately 48 hours after completion of cyclophosphamide
• Procedure: peripheral blood stem cell transplantation
  Occurs approximately 48 hours after completion of cyclophosphamide
• Radiation: image-guided radiation therapy
  Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.
• Radiation: intensity-modulated radiation therapy
  Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.
• Radiation: tomotherapy
  Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.

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 an 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; 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 exam with a 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
• Bilirubin of less than or equal to 1.5
• Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of normal
• Serum glutamic pyruvic 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
• DONOR: Donors will be excluded if for psychological or medical reasons they are unable to tolerate the procedure
• DONOR: 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%