Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies
Condition: Stem Cell Transplantation; Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Intervention: Thiotepa; Clofarabine; Busulfan; Allogeneic Stem Cell Transplantation; Thymoglobulin (ATG); G-CSF (Filgrastim); Tacrolimus; Methotrexate; Cyclophosphamide; Mesna
Intervention description: 5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8.; 40 mg/m^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3).; Test dose of 0.5 mg/kg through a central venous catheter (CVC)over 30 minutes on Day -7.
High dose 5,000 µMol-min through a central venous catheter (CVC) over 3 hours on Days -5, -4, and -3.; Infusion of stem cells through through a central venous catheter (CVC) On Day 0.; 1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3.; 5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal.; Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered as indicated after transplant day 90, if no GVHD is present. Tacrolimus is adjusted trough level of 5-15 ng/mL.; 5 mg/m2 by vein on Days 1, 3 and 6 and Day +11 post transplant. The Day 11 methotrexate dose may be held as indicated if mucositis is present.; Post haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4.; Post haploidentical stem cell transplant participants: 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses.
Intervention MeSH terms: Cyclophosphamide; Busulfan; Thiotepa; Methotrexate; Clofarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Cancer; Blood And Marrow Transplantation; Stem Cell; Leukemia; Lymphoma; Pediatrics; Bone marrow; Lymph node system; Allogeneic Stem Cell Transplant; ASCT; Busulfan; Busulfex; Myleran; Clofarabine; Clofarex; Clolar; Thiotepa; Antithymocyte globulin; ATG; Thymoglobulin; G-CSF; Filgrastim; Neupogen; Cyclophosphamide; Cytoxan; Neosar; Mesna; Mesnex; Tacrolimus; Prograf; Methotrexate

Summary:

      Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
      participant.

      The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine,
      when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical
      (bone marrow) stem cell transplantation can help to control cancers of the bone marrow and
      lymph node system. The safety of this treatment will also be studied.

      This is an investigational study. Thiotepa and clofarabine are FDA approved and commercially
      available for the treatment of leukemia. Busulfan is FDA approved and commercially available
      for use in stem cell transplantation. The combination of thiotepa, clofarabine, and busulfan
      together with a stem cell transplant is investigational.

      Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosed with one of the following diseases:

          2. Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission,
             or CR1 considered at risk for relapse

          3. Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS
             score) >/= 2 or myelodysplasia that has not responded to chemotherapy

          4. Biphenotypic leukemia

          5. Acute lymphocytic leukemia with induction failure, first complete remission with high
             risk cytogenetics (e.g. Philadelphia positive chromosome, t(4:11) Remission requiring
             more than 2 chemotherapy to achieve remission, or any stage beyond CR1

          6. Chronic Myelogenous Leukemia (CML): second chronic phase, accelerated phase or blast
             crises with less than 10% blasts in the bone marrow, or CR1 and resistance to Gleevec
             or other tyrosine kinase inhibitors

          7. Non-Hodgkin's Lymphoma - induction failures, second or third complete remission, or
             relapse (including relapse post autologous hematopoietic stem cell transplant)

          8. Hodgkin's disease - induction failure, second or later complete remission, or relapse
             (including relapse post autologous hematopoietic stem cell transplant).

          9. Chronic Lymphocytic Leukemia that has failed induction therapy or Rai Stages 2-4

         10. Related or unrelated donor which is HLA-matched or mismatched in 1 HLA A, B, C, DR, or
             DQ locus is acceptable (i.e. >/= 9/10 matched related or unrelated donor, matched with
             molecular high-resolution technique per current std. for BMT program). Cord blood
             units must match patient at 4, 5, or 6/6 HLA class 1 serological & II molecular
             antigens with a min. of 2 x 10e7 TNC/kg recipient weight in the pre-thawed fraction.
             For patient lacking a matched related or unrelated donor or acceptable cord blood
             unit(s), a related haploidentical donor (</= 7/8 allele matched at A, B, C, DR loci)
             may be used.

         11. Age </= 60 years.

         12. Lansky performance score >/= 50% for patients </= 16 years of age, or Zubrod
             performance status score of 0-2 for patients > 16 years of age.

         13. Cardiac function - left ventricular ejection fraction >/= 40%.

         14. Pulmonary function - diffusion capacity of at least 50% predicted. Children unable to
             perform pulmonary function tests (e.g. less than 7 years old) pulse oximetry of >/=
             92% on room air.

         15. Serum creatinine < 1.6 mg/dL or creatinine clearance >/= 50 ml/min.

         16. SGPT </= 200 IU/mL, serum bilirubin < 1.5 x normal.

         17. Written informed consent and assent as is age appropriate.

         18. No active infection.

        Exclusion Criteria:

          1. Pregnancy in women of child bearing potential (pregnancy test performed within 2 weeks
             of study entry).

          2. HIV positive (highly immunosuppressive treatment)

          3. Active CNS leukemia

          4. Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss
             with PI and strongly consider liver biopsy.