Randomized Double Cord Blood Transplant Study
Condition: Leukemia, Lymphocytic, Acute; Leukemia, Myelocytic, Acute; Leukemia, Myeloid, Chronic; Lymphoma, Non-Hodgkin
MeSH terms: Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute
Intervention: Expanded allogeneic cord blood (CB); One Unmanipulated and One Expanded Cord Blood Unit; Rituxan; Melphalan; Thiotepa; Fludarabine; Cyclophosphamide; Mesna; Total body irradiation (TBI)
Intervention description: Transplantation of Two Unmanipulated Cord Blood Units.; Transplantation of One Unmanipulated and One Expanded Cord Blood Unit.; 375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies.; 140 mg/m2 by vein on Day -8.; 5 mg/Kg by vein on Day -7.; 40 mg/m2 by vein on Days -6 to -3.; 50 mg/kg by vein on Day -6.; 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg).; Total body irradiation (TBI) given on Day -1 at 2 Gy.
Intervention MeSH terms: Cyclophosphamide; Melphalan; Thiotepa; Rituximab; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 1 Month
Maximum age: 80 Years
Healthy volunteers: No
Keywords: ALL; Leukemia, Lymphocytic, Acute; AML; Leukemia, Myelocytic, Acute; CML; Leukemia, Myeloid, Chronic; NHL; Lymphoma, Non-Hodgkin; double cord blood transplant; expanded cord blood transplant; Rituxan; Rituximab; Melphalan; Alkeran; Thiotepa; Fludarabine; Fludarabine phosphate; Fludara; Cyclophosphamide; Cytoxan; Neosar; Mesna; Mesnex

Summary:

      The goal of this clinical research study is to learn if combining cord blood units to make
      the cells "take" faster in recipients will help to improve the results of cord blood
      transplants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Disease-Specific Eligibility Requirements: Patients must have one of the following
             hematologic malignancies: 1. Acute Myelogenous Leukemia (AML), Myelodysplastic
             Syndrome (MDS) 2. Acute Lymphoblastic Leukemia (ALL) 3. Chronic Myelogenous Leukemia
             (CML) 4. Non-Hodgkin's Lymphoma (NHL) 5. Hodgkin's Disease (HD) 6. Chronic Lymphocytic
             Leukemia (CLL) 7. Chronic eosinophilic leukemia or Philadelphia chromosome negative
             CML.

          2. Greater than 1 month old and <=60 years old for full myeloablative therapy.

          3. Patients must have two CB units available which are matched with the patient at 4, 5,
             or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain
             at least 1E7 total nucleated cells/Kg recipient body weight in the pre-thawed
             fraction.

          4. Patient must be willing to undergo bone marrow harvest or peripheral blood progenitor
             cell (PBPC) collection for use in case of engraftment failure. If the patient is
             unable or fails to successfully undergo the collection, a family member must be
             identified to donate hematopoietic stem cells for haploidentical transplant in case of
             engraftment failure. If autologous hematopoietic stem cells cannot be procured due to
             marrow contamination by malignancy, or due to harvest failure, and a haploidentical
             relative is not available or not willing to donate, two cord blood units can be used
             as the back-up graft.

          5. Continuation to Criteria # 4: These units will be identified prior to enrollment in
             this study.

          6. Regimen 1 (Myeloablative mel/thiotepa/fludarabine): 1.Patients with ALL, HD, NHL, AML,
             MDS, CML, CLL and Chronic eosinophilic leukemia who are candidates for full
             myeloablative therapy. 2.Performance score of at least 60% by Karnofsky (age >= 12
             years), or Lansky Play-Performance Scale (age <12 years). 3.Age >=1 month <=60 years
             (high-dose).

          7. Continuation to Criteria # 6: 4.Adequate major organ system function as demonstrated
             by:a. Left ventricular ejection function of at least 40%. b.Pulmonary function test
             demonstrating a diffusion capacity of at least 50%. predicted (high-dose).
             c.Creatinine < 1.6 mg/dL. d.serum glutamate pyruvate transaminase (SGPT)/bilirubin <=
             to 2.0 x normal (high-dose).

          8. Eligibility for Regimen 2 (Non-myeloablative Cy-Flu-TBI): 1. Patients with ALL, AML,
             MDS, CML, NHL, CLL, Chronic eosinophilic leukemia and HD who are not candidates for
             full myeloablative therapy. All patients who received a prior autologous transplant
             are eligible. 2. Performance score of at least 60% by Karnofsky or PS < 3 (ECOG) (age
             >= 12 years), or Lansky Play-Performance Scale (age <12 years) 3. Age >= 1 month <=80
             years

          9. Continuation to Criteria # 8: 4. Left ventricular ejection function of at least 30%;
             5. Pulmonary function test demonstrating a diffusion capacity of at least 40%
             predicted; 6. Creatinine < 3.0 mg/dL; 7. SGPT <= to 4.0 x normal.

         10. Regimen 3 (Myeloablative VP16-TBI): 1. Patients with ALL who are candidates for
             myeloablative therapy, and require a TBI-containing regimen. 2. Performance score of
             at least 60% by Karnofsky or PS < 2 (ECOG) (age >= 12 years), or Lansky
             Play-Performance Scale (age <12 years). 3. Age >= 1 month <=50 years. 4. Organ
             function requirements: a. Left ventricular ejection function of at least 50%. b.
             Pulmonary function test demonstrating a diffusion capacity of at least 50% predicted.
             c. Creatinine < 1.6 mg/dL. d. SGPT <= 2.0 x normal.

        Exclusion Criteria:

          1. HIV positive.

          2. Pregnancy.

          3. Serious medical Condition.

          4. Patients with signs & symptoms leading to positive lumbar puncture (malignant cells in
             the CSF) or to documented metastatic parenchymal disease are ineligible for this
             study.

          5. Availability of appropriate, willing, HLA-matched related donor.