Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation
Condition: Myelodysplastic Syndromes; Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
Intervention: Clofarabine; Cytarabine; Thymoglobulin; Stem cell infusion
Intervention MeSH terms: Cytarabine; Clofarabine; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Conditioning regimens; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Allogeneic Stem Cell Transplantation; Nonmyeloablative conditioning; Clofarabine; Cytarabine; Anti-thymocyte globulin

Summary:

      This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a
      non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute
      myeloid leukemia undergoing allogeneic stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria (Patient):

          1. Myelodysplastic Syndrome (MDS), as defined by the World Health Organization criteria,
             OR Chronic Myelomonocytic Leukemia (CMML) as defined by the French American British
             classification OR Acute Myeloid Leukemia (AML) in complete remission [excluding
             FAB-M3] diagnosed by standard criteria and meet the criteria below:

               1. Patients may be in any CR

               2. No more than 2 cycles of consolidation. Any consolidation regimen may be used.

               3. No more than 6 months from documented CR to transplant.

          2. Age 18 years or older.

          3. ECOG performance status <=2

          4. Identification of suitable donor

          5. DLCO >=40% with no symptomatic pulmonary disease

          6. LVEF by MUGA >= 30%

          7. Serum creatinine <=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated
             glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the
             Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) =
             186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x
             (1.212 if patient is black).

          8. Bilirubin <=2 times the upper limit of normal

          9. AST <=3 times the upper limit of normal

        Donor criteria:

          1. HLA-Matched Sibling: The donor must be an adequate HLA match as determined by
             serologic typing for class (A, B) and low resolution molecular typing for class II
             (DRB1) as defined by institutional standards.

          2. Matched Unrelated Donor: An acceptable match per NMDP standards based on high
             resolution molecular typing.

          3. The donor must be healthy and must be an acceptable donor as per institutional
             standards for stem cell collection.

          4. The donor must have no significant cardiopulmonary, renal, endocrine, or hepatic
             disease.

          5. There is no upper age restriction for donors, but they must be at least 18 years of
             age.

          6. Syngeneic donors are not eligible.

          7. No known HIV.

        Exclusion Criteria:

          1. Pregnant or nursing.

          2. Active systemic infection considered opportunistic, life threatening or clinically
             significant at the time of treatment.

          3. Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled
             hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery
             disease, or symptomatic CNS involvement or psychiatric illness/social situations that
             would limit compliance with study requirements.

          4. Known HIV disease.

          5. History of other malignancy except for basal cell or squamous cell carcinoma of the
             skin or carcinoma in situ of the cervix or breast unless the subject has been off
             treatment and free from disease for > 3 years.

          6. Active disease at the time of transplant.