Rituximab to the Preparative Regimen of Etoposide and Total Body Irradiation in Acute Lymphoblastic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Etoposide; Total Body Irradiation; Rituximab
Intervention description: 60 mg/kg IV Daily Over 4 Hours for 1 Day; 3 Gy Daily for 4 Days; 375 mg/m^2 IV Weekly Over 4-8 Hours for 4 Weeks
Intervention MeSH terms: Rituximab; Etoposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Acute Lymphoblastic Leukemia; Leukemia; Total Body Irradiation; Etoposide; Rituximab; Rituxan; TBI; ALL

Summary:

      Primary Objective:

        -  To determine the progression free survival (PFS) of the preparative regimen rituximab,
           etoposide and total body irradiation (TBI), in patients with acute lymphoblastic
           leukemia (ALL) receiving allogeneic hematopoietic stem cell transplantation (SCT).

      Secondary Objectives:

        -  To determine the effect of rituximab on the incidence of acute graft vs. host disease
           (GVHD).

        -  To determine the efficacy of adding imatinib mesylate post transplant in ALL patients
           with the t(9;22)(q34;q11) cytogenetic abnormality.

        -  To estimate the probability of molecular complete remission at one year for the
           described treatment approach as determined by serial minimal residual disease (MRD)
           monitoring.

        -  To determine the rate of GVHD, engraftment, toxicity, and overall survival (OS) for this
           treatment regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with biopsy-proven ALL in remission or relapse.

          -  Adequate renal function, as defined by estimated serum creatinine clearance >50 ml/min
             and/or serum creatinine <1.8 mg/dL.

          -  Adequate hepatic function, as defined by aspartate aminotransferase (AST) or serum
             glutamic oxaloacetic transaminase (SGOT) <3 * upper limit of normal; serum bilirubin
             and alkaline phosphatase <2 * upper limit of normal, or considered not clinically
             significant.

          -  Adequate pulmonary function with Forced Expiratory Volume in One Second (FEV1), forced
             vital capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) at least 45% of
             expected corrected for hemoglobin.

          -  Adequate cardiac function with left ventricular ejection fraction at least 45%. No
             uncontrolled arrhythmias or symptomatic cardiac disease.

          -  Zubrod performance status <2.

          -  Patients must have a related, genotypically human leukocyte antigens (HLA) identical
             donor, or they must have a related or unrelated donor who is at least a 9/10 HLA match
             by high resolution typing.

          -  Female patient must not be pregnant and have negative pregnancy test.

          -  Patient and donor should be willing to participate in the study by providing written
             consent.

        Exclusion Criteria:

          -  Patients with unresolved grade 3 or greater non-hematologic toxicity from previous
             therapy. Patients with grade 2 toxicity will be eligible at the discretion of the
             principal investigator (PI).

          -  Patients with active central nervous system (CNS) disease.

          -  Evidence of acute or chronic active hepatitis or cirrhosis.

          -  Uncontrolled infection, including Human immunodeficiency virus (HIV) or Human
             T-lymphotropic virus Type I (HTLV-1) infection.

          -  Patients greater than 60 years-old.

          -  Prior autologous or allogeneic hematopoietic stem cell transplant.