Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation
Condition: Leukemia; Lymphoma; Allogeneic Haematopoietic Stem Cell Transplantation; Acute Lymphoblastic Leukemia
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Busulfan; Clofarabine; Thymoglobulin; Stem Cell Transplant
Intervention description: Test Dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.; 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors; Stem cell infusion on Day 0.
Intervention MeSH terms: Busulfan; Clofarabine; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 120.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Acute Lymphoblastic Leukemia; ALL; Acute lymphoblastic lymphoma; acute biphenotypic leukemia; Allogeneic hematopoietic cell transplantation; HCT; Stem Cell Transplant; Treatment-related mortality; Tyrosine kinase inhibitors; TKI; Busulfan; Busulfex; Myleran; Clofarabine; Clolar; Clofarex; Gleevec; Imatinib Mesylate

Summary:

      The goal of this clinical research study is to test the safety of giving clofarabine in
      combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in
      patients with advanced leukemia or lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic
             lymphoma, or acute biphenotypic leukemia in remission or relapse.

          2. Adequate renal function, as defined by estimated serum creatinine clearance >60
             ml/min.

          3. Bilirubin equal or less than 1.5 (unless Gilbert's Syndrome), serum glutamate pyruvate
             transaminase (SGPT) <3 X upper limit of normal and alkaline phosphatase <2 X upper
             limit of normal.

          4. Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced
             vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) at
             least 45% of expected corrected for hemoglobin. Children unable to perform pulmonary
             functions must have an oxygen saturation greater than 92% at room air.

          5. Adequate cardiac function with left ventricular ejection fraction at least 45% on
             appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac
             disease.

          6. Zubrod performance status <2 or Lansky/Karnofsky PS equal or greater to 70%.

          7. Patients must have a related, genotypically HLA identical donor, or they must have a
             unrelated donor who is 8/8 HLA match by high resolution typing.

          8. Patient or patient's legal representative, parent(s) or guardian should provide
             written informed consent. Assent of a minor if participant's age is at least seven and
             less than eighteen years.

          9. Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing
             potential defined as not post-menopausal for 12 months and no previous surgical
             sterilization.

        Exclusion Criteria:

          1. Patients with unresolved grade >2 non-hematologic toxicity from previous therapy.
             Patients with grade 2 toxicity will be eligible at the discretion of the PI.

          2. Patients with active central nervous system (CNS) disease.

          3. Evidence of acute or chronic active hepatitis or cirrhosis.

          4. Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.

          5. Patients greater than 65 years-old.

          6. Prior autologous or allogeneic hematopoietic stem cell transplant.