Total Marrow and Lymphoid Irradiation and Chemotherapy Before DSCT in Treating Patients With High-Risk ALL or AML

PRIMARY OBJECTIVES: I. Following a patient safety lead-in, evaluate the anti-tumor activity of the allogeneic hematopoietic cell transplant (alloHCT) preparative regimen - TMLI, cyclophosphamide (Cy) and etoposide (VP-16), as assessed by 2-year progression-free survival (PFS).

SECONDARY OBJECTIVES: I. Estimate overall survival (OS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

II. Evaluate early and late toxicities/complications by organ and severity, and characterize by organ dose/dose volume, including acute/chronic graft-versus-host-disease (GVHD), infection, and longer-term complications (via protocol #s 07173 and 00029).

OUTLINE: Patients undergo image guided TMLI on days -9 to -5, receive etoposide intravenously (IV) on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

After completion of study treatment, patients are followed up for 5 years.

Inclusion criteria

• Participant has the ability and the willingness to sign the informed consent document (for adults only, for participants with mild cognitive abilities may use a legally authorized representative)
• Documented (signed) informed consent; the patient, family member and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent forms
• Karnofsky performance status >= 70% =< 2
• Acute lymphocytic leukemia or acute myelogenous leukemia who are not in first remission or second remission i.e. after failing induction therapy, or in relapse or beyond second remission; (prior therapy with VP-16 and Cytoxan is allowed)
• All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings 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 killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable
• The time from the end last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days from planned start of study treatment; Note: Chemotherapy given within 14 days of planned study enrollment for the purpose of controlling counts is permitted
• Total bilirubin =< 1.5 x upper limit of normal (ULN) OR 3 x ULN for Gilbert's disease
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x ULN
• Measured creatinine clearance >= 80 ml/min per 24 hour urine collection OR serum creatinine =< 1.3 mg/dL
• Women of child bearing potential only: Negative urine or serum pregnancy test
• Pulmonary function tests: Forced expiratory volume in one second (FEV1) and carbon monoxide diffusion capacity (DLCO) (adjusted for Hb) >= 50% adjusted of predicted normal value
• Echocardiogram (ECHO) or multi gated acquisition scan (MUGA): ejection fraction of >= 50% AND no finding of abnormal wall motion (i.e. report does not indicate that wall motion is "abnormal" or "altered")
• Electrocardiogram (EKG) showing no ischemic changes and no abnormal rhythm
• Agreement of men AND women-of-child-bearing-potential to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• DONOR ELIGIBILITY: Donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP)

Exclusion criteria

• Prior autologous or allogeneic hematopoietic stem cell
• Prior radiation therapy that would exclude the use of TMLI
• Plans during the trial to receive any other (non-trial) investigational agents, or concurrent biological, chemotherapy, or radiation therapy; (chemotherapy for white blood count control is permitted)
• Uncontrolled illness including ongoing or active infection
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to etoposide
• Patients with other active malignancies are ineligible for this study, other than localized malignancies
• Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
• Women who are planning to become pregnant or breast feed during the trial
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study