Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
Condition: Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: busulfan; cyclophosphamide; cytarabine; radiation therapy; Etoposide; Stem Cell Transfusion
Intervention description: Given orally 1mg/kg/dose (or 40mg/m2/dose for young children); Given IV; Given IV; Patients undergo total body irradiation; infusion
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Busulfan; Etoposide; Etoposide phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Maximum age: 55 Years
Healthy volunteers: No
Keywords: adult acute myeloid leukemia in remission; childhood acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 3 follicular lymphoma; secondary acute myeloid leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent mantle cell lymphoma; refractory anemia with ringed sideroblasts; refractory anemia; chronic myelomonocytic leukemia; refractory cytopenia with multilineage dysplasia; previously treated myelodysplastic syndromes; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; relapsing chronic myelogenous leukemia; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; juvenile myelomonocytic leukemia; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell
      transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's
      immune system from rejecting the donor's stem cells. When the stem cells from a related
      donor, that do not exactly match the patient's blood, are infused into the patient they may
      help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
      platelets.

      PURPOSE: This phase II trial is studying how well giving chemotherapy with or without
      radiation therapy followed by donor stem cell transplant works in treating patients with
      hematologic cancer.
    

Eligibility criteria:

        Eligibility Criteria:

          1. Patients with histologic confirmation of the following diseases are eligible:

               1. AML in first, second or greater remission

               2. AML in early relapse, defined at <30% marrow blasts

               3. ALL in second or greater complete remission

               4. High risk ALL in first complete remission, with high risk being defined by the
                  presence of t(4;11), t(9;22), or t(8;14) translocation, or patients presenting
                  with extreme hyperleukocytosis (initial WBC >500 K/ml) or failure to achieve a
                  complete remission after standard induction therapy.

               5. CML

               6. Myelodysplastic syndromes (including evolution to AML, e.g., Refractory Anemia
                  with Excess Blasts (RAEB), or Refractory Anemia with Excess Blasts in
                  transformation (RAEB-t).

               7. Lymphoma (intermediate and high grade) chemosensitive (CR or PR) after first or
                  greater relapse or chemosensitive to first line therapy but only achieving PR.

               8. Hematologic Disease and Inherited Immunodeficiencies

               9. Hodgkin's disease, relapsed or refractory to standard treatments.

          2. Patients must be less than or equal to 55 years of age.

          3. Patients (or guardians if minor) must be able to give informed consent. Children older
             than 11 years of age must assent to the process.

          4. Patients or their guardians must demonstrate proof-of-payment.

          5. Patients must have an ECOG Performance Status of 2 or less. (See Appendix I)

          6. Patients must have no evidence of active infection at the time of transplantation.

          7. Patients must be HIV nonreactive.

          8. Patients must have a pre-transplant, multi-organ assessment prior to transplantation
             with the following outcome:

               1. resting ejection fraction of 50% or greater (or shortening fraction greater than
                  28% for small children).

               2. Diffusion capacity of 50% or greater of predicted, a FEV1 of 50% or greater, and
                  a P2O of 80 mm Hg as demonstrated on pulmonary function testing.

               3. serum creatinine of less than or equal to 2.0 mg/dL and/or a corrected creatinine
                  clearance of 50 ml/min or greater on 24 hr urine.

               4. A total bilirubin of less than 2.5 mg/dL and an AST less than 4 times the upper
                  limits of normal.

          9. Females who are childbearing age may not be pregnant or lactating and must have a
             current negative pregnancy test

        Ineligibility Criteria:

          -  Patients who have a life expectancy of less than three months with therapy.

          -  Patients who have an ECOG performance status greater than 2, (See Appendix I) or
             Lansky Scale < 70%.

          -  Patients who have angina and/or congestive heart failure requiring treatment, or who
             have had a myocardial infarction within the past year.

          -  Patients who have a resting ejection of less than 50% (or shortening fraction less
             than 28%) and who have not been cleared for transplant by cardiology

          -  Patients who have severe renal disease as demonstrated by a serum creatinine greater
             than 2.0 mg/dL and/or a corrected creatinine clearance less than 50 ml/min. (corrected
             for BSA of 1.73 m¬2)

          -  Patients who have had any complication that makes the risk of death during
             transplantation from non-malignant causes greater than the risk of relapse.

          -  Patients who have any active infection such as a soft tissue infection, sinus
             infection, dental infection, fungal infection or hepatitis including chronic active
             hepatitis; if the infection is successfully treated, the patient may be reconsidered
             for transplantation at a later date.

          -  Patients who have decreased pulmonary function due to any disorder as demonstrated by
             a diffusion capacity of less than 50% of predicted, a FEV1 of less than 50% of
             predicted or a PO2 of less than 80 mm Hg pulmonary function testing.

          -  Patients who have decreased liver function as demonstrated by a total bilirubin of
             greater than 2.5 mg/dL and/or an AST greater than 4 times the upper limits of normal.

          -  Patients who have diabetes mellitus will be considered on a case-by-case basis.
             However, patients with diabetes who are not controlled by medical management will be
             ineligible.

        -Patients who have a significant psychiatric illness will be considered on a case- by-case
        basis. With the patient's consent, their Mental Health Care worker will assist the managing
        transplant physicians in determining if the patient can safely undergo transplantation and
        comply with followup recommendations.

          -  Psychosocial assessment by the bone marrow transplant team may identify individuals
             for whom this form of therapy may be contraindicated. This decision will be based upon
             estimated adequacy of patient support systems and prediction of patient's compliance
             with medications, required diagnostic procedures and/or follow-up care.

          -  Females who are childbearing age may not be pregnant or lactating and must have a
             current negative pregnancy test

          -  Patients who had a stem cell transplant less than one year earlier