New York, New York 10065

  • Myelodysplastic Syndromes

Purpose:

RATIONALE: Giving high-dose chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with total-body irradiation and donor umbilical cord blood transplant works in treating patients with hematologic cancer or other disease.


Study summary:

OBJECTIVES: Primary - Determine, preliminarily, the efficacy of double-unit umbilical cord blood (UCB) transplantation (UCBT) in patients with hematologic malignancy. Secondary - Determine the incidence and rate of donor-derived neutrophil and platelet recovery in these patients. - Determine the contribution of each unit of UCB to initial and sustained engraftment in these patients. - Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days in these patients. - Determine the incidence and severity of chronic GVHD at 1 year in these patients. - Determine the incidence of treatment-related mortality at 100 and 180 days in these patients. - Determine the incidence of malignant relapse in these patients. - Determine the incidence of serious infectious complications in these patients. - Determine immune recovery after UCBT and correlate with serious infectious complications in these patients. - Determine the probabilities of overall and disease-free survival of these patients at 2 years after UCBT. - Determine the performance of double-unit correlative laboratory studies and correlate with engraftment of each unit in these patients. OUTLINE: - Myeloablative preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -5 and cyclophosphamide IV over 30-60 minutes on days -6 and -5. Patients also undergo total-body irradiation 3 times daily on days -3 to -1 and twice on day 0. - Umbilical cord blood (UCB) transplantation: Patients receive UCB IV over 20-60 minutes on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover. - Graft-vs-host (GVHD) prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally every 8-12 hours on days -3 to 100 and mycophenolate mofetil IV or orally twice daily on days -3 to 45. Blood samples and bone marrow aspirates are collected at baseline and periodically during and after completion of study treatment. Samples may be examined for engraftment, chimerism analysis, cytogenetic analysis, recovery of natural killer cells, and immune recovery. Lymphoid immunophenotyping and function is also determined. UCB units are examined by flow cytometry and killer immunoglobulin-like receptor (KIR) genotype analysis. After completion of study therapy, patients are followed periodically for at least 2 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.


Criteria:

DISEASE CHARACTERISTICS: - Diagnosis of one of the following: - Acute myeloid leukemia (AML) meeting 1 of the following criteria: - Complete first remission (CR1) at high risk for relapse, defined by 1 of the following: - Known prior diagnosis of myelodysplastic syndromes (MDS) - Therapy-related AML - WBC > 100,000/mm³ - Presence of extramedullary leukemia at diagnosis - Unfavorable FAB type (M0, M5-7) - High-risk cytogenetics (those associated with MDS, abnormalities of Philadelphia chromosomes 5, 7, or 8, or complex karyotype) - Required ≥ 2 inductions to achieve CR1 - Complete second remission (CR2) - No AML ≥ CR2 - Acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria: - CR1 at risk for relapse, defined by 1 of the following: - WBC > 100,000/mm³ (< 18 years old) OR > 50,000/mm³ (≥ 18 years old) - Presence of extensive extramedullary disease (excluding CNS disease) - Presence of high-risk cytogenetic abnormality, such as t(9;22), t(1;19), t(4;11), or other myelomonocytic leukemia rearrangements (11q23) or t(8;14) (excluding blastic-phase ALL in pediatric patients) - Failed to achieve complete remission after 4 weeks of induction therapy - CR2 or complete third remission (CR3) - Not > CR3 - Acute undifferentiated leukemia, infant leukemia, or biphenotypic leukemia in CR1, CR2, or CR3 - Patients with infant leukemia must be able to receive total-body irradiation - Not > CR3 - Juvenile myelomonocytic leukemia with < 30% bone marrow blasts - Chronic myelogenous leukemia meeting the following criteria: - Failed prior imatinib mesylate AND in first or second chronic phase or accelerated phase - Not in blast crisis - MDS meeting the following criteria: - Low (score 0) International Prognostic Scoring System (IPSS) score with life threatening cytopenia or red cell or platelet-transfusion dependent OR intermediate (score 1) or high (score 2) IPSS score - Patients with bone marrow blasts ≥ 10% should have AML induction therapy with disease response to < 5% blasts and at least partial count recovery - No MDS with ≥ 10% bone marrow blasts refractory to chemotherapy - Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria: - High-grade disease in first partial remission (PR) after initial therapy with biopsy-proven residual disease that is not appropriate for further chemotherapy or autologous stem cell transplantation - High-grade or diffuse large cell NHL with recurrent disease after first remission with chemosensitivity as evidenced by at least PR (defined as > 50% reduction in mass size after therapy) - No NHL refractory to chemotherapy (less than PR after ≥ 2 regimens) - No AML evolved from myelofibrosis - Not a candidate for autologous stem cell transplantation - No active CNS leukemia - No bone marrow aplasia (bone marrow cellularity < 5%) - No acute leukemia with any of the following: - Morphologic relapse or persistent disease in the bone marrow (cytogenetic relapse without morphologic evidence of relapse or cytogenetic persistent disease in the bone marrow is allowed) - Active extramedullary leukemia - Required > 2 courses of chemotherapy to obtain present remission status - No suitably HLA matched related or unrelated volunteer donor available - Double-unit umbilical cord blood units must meet the following criteria: - At least 4 of 6 HLA-A and B antigen and DRB1 allele matched with recipient - At least 3 of 6 HLA-A, B, and DRB1 matched to each other - Cryopreserved dose of ≥ 1.5 x 10^7 total nucleated cells/recipient body weight NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: - Karnofsky performance status (PS) 70-100% (age ≥ 16 years) OR Lansky PS 70-100% (age < 16 years) - Creatinine clearance ≥ 60 mL/min OR creatinine < 1.5 mg/dL - Bilirubin < 2.5 mg/dL (unless Gilbert's syndrome) - ALT and AST < 3 times upper limit of normal - Albumin ≥ 2.5 g/dL - LVEF ≥ 50% - DLCO ≥ 60% - No uncontrolled viral, bacterial, or fungal infection - Not HIV positive - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No prior autologous or allogeneic hematopoietic stem cell transplantation - No prior radiation therapy rendering the patient ineligible for total-body irradiation


NCT ID:

NCT00388102


Primary Contact:

Study Chair
Juliet Barker, MBBS
Memorial Sloan-Kettering Cancer Center


Backup Contact:

N/A


Location Contact:

New York, New York 10065
United States

Juliet Barker, MBBS
Phone: 212-639-3468

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: December 08, 2022

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