Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Clofarabine; Cyclosporine; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Peripheral Blood Stem Cell Transplantation; Pharmacological Study; Total-Body Irradiation
Intervention description: Undergo allogeneic hematopoietic PBSCT; Given IV; Given PO; Correlative studies; Given PO; Undergo allogeneic hematopoietic PBSCT; Optional correlative studies; Undergo TBI
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Clofarabine; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: In part 1, patients are treated at each dose in cohorts of three and observed for any dose limiting toxicities. In Part 2, patients are treated at the maximum tolerated dose established in Part 1.
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well clofarabine works when given
      together with low-dose total-body irradiation (TBI) in treating patients with acute myeloid
      leukemia (AML) undergoing donor peripheral blood stem cell transplant (PBSCT). Giving
      chemotherapy and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also
      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients age >= 55 years with AML OR patients age < 55 years with AML, who also
             through pre-existing medical conditions or prior therapy are considered to be at high
             risk for serious toxicities associated with a conventional, high-dose preparative
             regimen

          -  Patients must be in morphologic leukemia-free state (marrow blasts < 5%) without
             evidence of extramedullary disease within 21 days of HCT

          -  Only patients with Relapse Risk Score > 0 ("high risk") will be enrolled during Part
             1; patients with all Relapse Risk Scores will be enrolled during Part 2 (low risk
             group terminated August 2014)

          -  HLA-identical related or HLA-matched unrelated donor available

          -  A signed informed consent form or minor assent form

          -  DONOR: FHCRC matching allowed will be grade 1.0 to 2.1: unrelated donors who are
             prospectively: matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only
             a single allele disparity will be allowed for HLA-A, B, or C as defined by high
             resolution typing

          -  DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion;
             donors are excluded when preexisting immunoreactivity is identified that would
             jeopardize donor hematopoietic cell engraftment; this determination is based on the
             standard practice of the individual institution; the recommended procedure for
             patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel
             reactive antibody (PRA) screens to class I and class II antigens for all patients
             before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell
             cytotoxic cross matches should be obtained; the donor should be excluded if any of the
             cytotoxic cross match assays are positive; for those patients with an HLA Class I
             allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be
             obtained regardless of the PRA results

          -  DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a
             two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this
             type of mismatch is not allowed

          -  DONOR: Peripheral blood stem cells (PBSC) only will be permitted as a HSC source on
             this protocol

        Exclusion Criteria:

          -  AML French-American-British (FAB) M3 in first complete remission (CR1)

          -  Active AML involvement of the central nervous system (CNS) with disease refractory to
             intrathecal chemotherapy

          -  Presence of circulating leukemic blasts in the peripheral blood detected by standard
             morphology

          -  Patients who are human immunodeficiency virus (HIV)+ (HIV+ patients registered at Fred
             Hutchinson Cancer Research Center [FHCRC] should be offered treatment on Protocol
             1410)

          -  Fertile men and women unwilling to use contraceptive techniques during and for 12
             months following treatment

          -  Left ventricular ejection fraction < 35% (or, if unable to obtain ejection fraction,
             shortening fraction of < 26%); ejection fraction is required if age > 50 years or
             there is a history of anthracycline exposure or history of cardiac disease; patients
             with a shortening fraction < 26% may be enrolled if approved by a cardiologist

          -  Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% (corrected), total
             lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or
             receiving supplementary continuous oxygen

          -  The FHCRC principal investigator (PI) of the study must approve enrollment of all
             patients with pulmonary nodules

          -  Patients with clinical or laboratory evidence of liver disease will be evaluated for
             the cause of liver disease, its clinical severity in terms of liver function, and the
             degree of portal hypertension; patients will be excluded if they are found to have
             fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension,
             alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices,
             hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by
             prolongation of the prothrombin time, ascites related to portal hypertension, bridging
             fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral
             hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease

          -  Serum creatinine should be within normal limits as specified by institutional
             guidelines; for patients with serum creatinine > upper limit of normal, a 24-hour
             creatinine clearance will be performed and should be equal to or more than the lower
             limit of normal

          -  Karnofsky score < 60 or Lansky score < 50

          -  Patients with poorly controlled hypertension and on multiple antihypertensives

          -  Females who are pregnant or breastfeeding

          -  Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
             or those with non-hematologic malignancies (except non-melanoma skin cancers) who have
             been rendered with no evidence of disease, but have a greater than 20% chance of
             having disease recurrence within five years; this exclusion does not apply to patients
             with non-hematologic malignancies that do not require therapy

          -  The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine
             kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose
             cytarabine, chlorambucil, or Rituxan will not be allowed within three weeks of the
             initiation of conditioning

          -  Fungal infections with radiological progression after receipt of amphotericin B or
             active triazole for greater than 1 month

          -  Patients with active bacterial or fungal infections unresponsive to medical therapy

          -  DONOR: Marrow donors

          -  DONOR: Donors who are HIV-positive and/or medical conditions that would result in
             increased risk to the donor filgrastim (G-CSF) mobilization and PBSC collections

          -  DONOR: Identical twin

          -  DONOR: Any contraindication to the administration of subcutaneous G-CSF at a dose of
             16 mg/kg/day for 5 consecutive days

          -  DONOR: Serious medical or psychological illness

          -  DONOR: Pregnant or lactating females

          -  DONOR: Prior malignancy within the preceding 5 years, with the exception of
             non-melanoma skin cancers

          -  DONOR: Children < 12 years old