Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Condition: Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukaemia With Prior Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3)(Q21Q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9); Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With T(1;19)(Q23;P13.3); E2A-PBX1 (TCF3-PBX1); Ph+ ALL; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma; Hematopoietic Cell Transplant Recipient
MeSH terms: Burkitt Lymphoma; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Mantle-Cell; Hematologic Neoplasms; Lymphoma, Large-Cell, Anaplastic; Leukemia, Erythroblastic, Acute; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Syndrome; Recurrence
Intervention: Cyclophosphamide; Filgrastim; Fludarabine Phosphate; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Total-Body Irradiation
Intervention description: Given IV; Given SQ; Given IV; Given PO; Undergo PBSC; Undergo PBSC; Given IV or PO; Undergo total-body irradiation (TBI)
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Healthy volunteers: No

Summary:

      This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works
      in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus
      and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host
      disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of
      bone marrow from half-matched (haploidentical) donors. This approach has extended the
      transplant option to patients who do not have matched related or unrelated donors, especially
      for patients from ethnic minority groups. The graft contains cells of the donor's immune
      system which potentially can recognize and destroy the patient's cancer cells
      (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune
      system is prevented by giving low doses of chemotherapy (fludarabine phosphate and
      cyclophosphamide) and total-body irradiation before transplant. Patients can experience low
      blood cell counts after transplant. Using stem cells and immune cells collected from the
      donor's circulating blood may result in quicker recovery of blood counts and may be more
      effective in treating the patient's disease than using bone marrow.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Molecular based human leukocyte antigen (HLA) typing will be performed for the HLA-A,
             -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity;
             a minimum match of 5/10 is required; an unrelated donor search is not required for a
             patient to be eligible for this protocol if the clinical situation dictates an urgent
             transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood
             of finding a matched, unrelated donor

          -  Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < 5%
             blasts with no morphological characteristics of acute leukemia (e.g., Auer rods) in a
             bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul,
             including patients in complete remission with incomplete platelet recovery (CRp); if
             the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has
             < 5% blasts, an exception may be made to include this patient up to principal
             investigator (PI) discretion

          -  Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by
             at least one of the following:

               -  Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11),
                  mixed lineage leukemia (MLL) rearrangements

               -  White blood cell counts > 30,000/mcL

               -  Patients over 30 years of age

               -  Time to complete remission > 4 weeks

               -  Presence of extramedullary disease

               -  Minimal residual disease

               -  Other risk factors determined by the patient's attending physician to be high
                  risk features requiring transplantation

          -  Acute myelogenous leukemia in high risk CR1 as defined by at least one of the
             following:

               -  Greater than 1 cycle of induction therapy required to achieve remission

               -  Preceding myelodysplastic syndrome (MDS)

               -  Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities

               -  French-American-British (FAB) M6 or M7 leukemia, or

               -  Adverse cytogenetics for overall survival such as:

                    -  Those associated with MDS

                    -  Complex karyotype (>= 3 abnormalities); or

                    -  Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with
                       other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)],
                       t(11;19)(q23;p13.1)]

               -  Other risk factors determined by the patient's attending physician to be high
                  risk features requiring transplantation

          -  Acute leukemias in second (2nd) or subsequent remission

          -  Biphenotypic/undifferentiated leukemias in first (1st) or subsequent complete
             remission (CR)

          -  High-risk MDS status-post cytotoxic chemotherapy

          -  Burkitt's lymphoma: second or subsequent CR

          -  Chemotherapy-sensitive (at least stable disease) large cell, mantle cell or Hodgkin's
             lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and
             are ineligible for an autologous transplant

          -  Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at
             least two prior therapies (excluding single agent Rituxan)

          -  Multiple myeloma (MM) stage II or III patients who have progressed after an initial
             response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT)
             or MM patients with refractory disease who may benefit from tandem
             autologous-nonmyeloablative allogeneic transplant

          -  Left ventricular ejection fraction at rest must be >= 35%

          -  Bilirubin =< 2.5 mg/dL

          -  Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) < 5 x ULN

          -  Alkaline phosphatase < 5 x ULN

          -  Serum creatinine within normal range for age, or if serum creatinine outside normal
             range for age, then renal function (creatinine clearance or glomerular filtration rate
             [GFR]) > 40 mL/min/1.73m^2

          -  Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion
             capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected
             for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2)
             saturation > 92% on room air

          -  Karnofsky/Lansky score >= 60%

          -  Patients who have received a prior allogeneic HSCT and who have either rejected their
             grafts or who have become tolerant of their grafts with no active GVHD requiring
             immunosuppressive therapy

          -  Patients will undergo standard pre-transplant work-up as dictated by standard practice
             guidelines the results of which may be used for screening for this study

          -  DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient;
             eligible donors include biological parents, siblings, or children, or half-siblings

          -  DONOR: Age >= 12 years

          -  DONOR: Weight >= 40 kg

          -  DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a
             vascular access device; vein check must be performed and verified by an apheresis
             nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)

          -  DONOR: Donors must meet the selection criteria as defined by the Foundation for the
             Accreditation of Cell Therapy (FACT) and will be screened per the American Association
             of Blood Banks (AABB) guidelines

        Exclusion Criteria:

          -  HLA-matched or single allele-mismatched donor able to donate

          -  Pregnancy or breast-feeding

          -  Current uncontrolled bacterial, viral or fungal infection (currently taking medication
             with evidence of progression of clinical symptoms or radiologic findings)

          -  Patients with primary idiopathic myelofibrosis

          -  DONOR: Positive anti-donor HLA antibody