Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib
Condition: Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Blastic Phase; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase of Disease; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Disease
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Recurrence
Intervention: Cyclosporine; Dasatinib; Fludarabine Phosphate; Imatinib Mesylate; Mycophenolate Mofetil; Nilotinib; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Therapeutic Allogeneic Lymphocytes; Total-Body Irradiation
Intervention description: Given IV or PO; Given PO; Given IV; Given PO; Given PO; Given PO; Undergo nonmyeloablative allogeneic PBSC transplantation; Undergo allogeneic PBSC transplantation; Given IV; Undergo TBI
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Imatinib Mesylate; Dasatinib; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well fludarabine phosphate and total-body irradiation
      followed by donor peripheral blood stem cell transplant work in treating patients with acute
      lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous
      treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy,
      such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral
      blood stem cell transplant helps stop the growth of cancer cells. It may also stop the
      patient's immune system from rejecting the donor's stem cells. The donated stem cells may
      replace the patient's immune system and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
      infusion) after the transplant may help increase this effect. Sometimes the transplanted
      cells from a donor can also make an immune response against the body's normal cells. Giving
      mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients =< 12 years of age must be approved by Fred Hutchinson Cancer Research Center
             (FHCRC) principal investigator (PI) in advance

          -  Patients with a history of Ph+ ALL or CML-BC who, after receiving imatinib mesylate,
             (or either dasatinib or nilotinib) have < 15% blasts on morphologic marrow evaluation;
             patients with no detectable Ph+ ALL by morphologic or molecular assays (complete
             remission) will be accepted

          -  An appropriately human leukocyte antigen (HLA) matched related or unrelated donor must
             be prospectively identified who will be available to donate filgrastim (G-CSF)
             mobilized stem cells

          -  RELATED DONOR:

               -  Related donor who is HLA genotypically identical at least at one haplotype and
                  may be genotypically or phenotypically identical at the allele level at HLA-A,
                  -B, -C, -DRB1, and -DQB1;

               -  Donor must consent to G-CSR administration and leukapheresis;

               -  Donor must have adequate veins for leukapheresis or agree to placement of central
                  venous catheter (femoral, subclavian)

          -  HLA-MATCHED UNRELATED DONOR:

               -  FHCRC matching allowed will be grades 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

               -  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

               -  Patient and donor pairs homozygous at a mismatched allele in the graft rejection
                  vector 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

               -  Only G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol

        Exclusion Criteria:

          -  Central nervous system (CNS) involvement with leukemia refractory to intrathecal
             chemotherapy; prior to HSCT (all patients must receive a diagnostic lumbar puncture
             (LP) with intrathecal (IT) chemotherapy as per standard practice)

          -  Fertile men or women unwilling to use contraceptive techniques during and for 12
             months following treatment

          -  Patients with active non-hematologic malignancies (except non-melanoma skin cancers);
             this exclusion does not apply to patients with non-hematologic malignancies that do
             not require therapy

          -  Patients with a history of non-hematologic malignancies (except non-melanoma skin
             cancers) currently in a complete remission, who are less than 5 years from the time of
             complete remission, and have a > 20% risk of disease recurrence; this exclusion does
             not apply to patients with non-hematologic malignancies that do not require therapy

          -  Females who are pregnant or breastfeeding

          -  Patients who are human immunodeficiency virus (HIV)-positive

          -  Patients with poorly controlled hypertension despite multiple antihypertensives

          -  Adults: Karnofsky score < 60

          -  Pediatrics: Lansky play-performance score < 40

          -  Patients with cardiac 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

          -  Diffusing capacity of the lungs for carbon monoxide (DLCO) < 30%

          -  Total lung capacity (TLC) < 30%

          -  Forced expiratory volume in one second (FEV1) < 30% and/or receiving supplementary
             continuous oxygen; the FHCRC PI of the study must approve enrollment of all patients
             with pulmonary nodules

          -  Patients with clinical or laboratory evidence of liver disease would 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,
             bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with
             total serum bilirubin > 3 mg/dL, or symptomatic biliary disease

          -  Creatinine levels more than 2.2 X's the upper limit of normal (ULN) at the laboratory
             where the analysis was performed

          -  Patients with active bacterial or fungal infections unresponsive to medical therapy

          -  For patients receiving dasatinib or nilotinib, baseline corrected QT interval (QTc)
             (Fridericia's method) prolongation greater than 500 msec

          -  RELATED DONORS:

               -  Identical twin

               -  Infection with HIV

               -  Inability to achieve adequate venous access

               -  Known allergy to G-CSF

               -  Current serious system illness

               -  Bone marrow (BM) donors

          -  HLA-MATCHED UNRELATED DONORS:

               -  BM donors

               -  Donors who are HIV-positive and/or, medical conditions that would result in
                  increased risk for G-CSF mobilization and harvest of PBSC