Hematopoietic Stem Cell Transplantation (HSCT) Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit
Condition: Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; Leukemia, Myelocytic, Acute; Leukemia, Myeloid, Chronic; Lymphoma, Non-Hodgkin; Lymphoma, Hodgkins
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Hodgkin Disease
Intervention: Haploidentical/cord transplant
Intervention description: Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation.
Conditioning Regimens Choice of regimen at the discretion of the treating physician
Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1)
Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1)
Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Unrelated Umbilical Cord Blood Transplant(UCB); CD34+ Selected mismatched related donor; Haploidentical donor; hematopoietic stem cell transplantation(HSCT); ALL; Leukemia, Lymphocytic, Acute; AML; Leukemia, Myelocytic, Acute; CML; Leukemia, Myeloid, Chronic; NHL; Lymphoma, Non-Hodgkin; HL; Lymphoma, Hodgkins

Summary:

      This study is a means of providing transplantation to those patients who would be a stem cell
      transplant candidate who do not have an appropriate donor.

      The use of CD34 selected haploidentical donor with an umbilical cord unit may help provide
      earlier engraftment without the need for long term immunosuppression.

      This study tests a new method of bone marrow transplantation called combined
      haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells
      (the stem cells) from a partially human leukocyte antigen (HLA) matched (haploidentical)
      related donor are collected from the blood, as well as cells from an umbilical cord are
      transplanted into the patient (the recipient) after administration of a "conditioning
      regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the
      entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and
      suppress the recipient's immune system to allow the transplanted cells to take (grow).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients between 18 and 65 years old

          -  Patient has a related family member(haploidentical) or unrelated which is 5 of 10 HLA
             identical match.

        Standard Risk

          -  Acute myelogenous leukemia: CR1 with high risk cytogenetics or molecular abnormalities
             such as FLT-3 ITD, or CR2 with a first remission that must have lasted > 1 year.

          -  Acute Lymphocytic Leukemia: CR1, in order to be standard risk must NOT have
             Philadelphia Chromosome.

          -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory
             to fludarabine or fail to have a complete or partial response after therapy with a
             regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin)
             or experience disease relapse within 12 months after completing therapy with a regimen
             containing fludarabine (or another nucleoside analog).

          -  Chronic myelogenous leukemia: resistant to or intolerant of TKI, in CP1 or CP2, or
             with a mutation that suggests resistance to TKI.

          -  Myelodysplastic Syndrome: RA, RARS, must be IPSS ≥ INT-2, Blasts <5%.

        High Risk Patients:

          -  Acute myelogenous leukemia: Patients with CR2 are considered high risk if they have
             high risk cytogenetics, or molecular abnormalities or CR1 lasted for less than 1 year.
             Any evidence of active disease or no blasts in an acellular marrow.

          -  Acute Lymphocytic Leukemia: CR1- with Ph+ disease, CR2/+ with any cytogenetics. Any
             evidence of active disease.

          -  Chronic myelogenous leukemia- CP2/+, AP1/+, resistant or intolerant to TKI.

          -  Hodgkin's or Non Hodgkin's lymphoma- Disease recurrence following an autologous
             transplant, or high risk disease not thought to benefit from autologous transplant.

          -  Chronic lymphocytic leukemia- that is resistant to fludarabine, and never has been in
             remission or with stable disease/progressive disease

          -  Multiple myeloma: Must have had prior treatment. Patients in CR2 or greater can be
             considered, must have already failed autologous transplant Previous autologous
             transplant,must have been greater than 6 months prior to undergoing this transplant.

          -  Myelodysplastic syndrome: RAEB

          -  Other Myeloproliferative disorders including myelofibrosis, spent phase p
             Vera,Essential thrombocytosis,CMML.

        Exclusion Criteria:

          -  Patients <18 years old Disease related criteria

          -  APML, presence of t(15,17) in first CR

          -  Patients with good risk AML, for example t(8;21), or inv 16, or normal cytogenetics
             with FLT-3-ITD negative, NPM-1 positive disease in 1st CR

          -  MDS IPSS < INT-2 Miscellaneous Criteria

          -  Recipients who have a matched related sibling or unrelated donor

          -  If recipient has evidence of anti-HLA antibodies directed against cord or haplo-donor
             as determined byflowPRA.

        Underlying health criteria:

          -  Zubrod performance status > 2 (see Appendix E)

          -  Life expectancy is limited to less than 8 weeks by concomitant illness

          -  Patients with severely decreased LVEF (EF < 40%)

          -  Impaired pulmonary function tests (PFT's) (FVC, FEV1, DLCO < 45% predicted)

          -  Estimated Creatinine Clearance <50 ml/min

          -  Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal

          -  Evidence of chronic active hepatitis or cirrhosis

          -  HIV-positive

          -  Patient is pregnant

          -  Patient or guardian not able to provide informed consent