RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy or radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy, radiation therapy, and umbilical cord blood transplantation in treating patients who have hematologic cancer.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma	Drug: anti-thymocyte globulin  Drug: busulfan  Drug: cyclosporine  Drug: melphalan  Drug: methylprednisolone	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the rates of hematologic and immune reconstitution in pediatric patients with high risk hematologic malignancies in first remission or in second or subsequent remission, and adult patients with acute lymphocytic leukemia (ALL) or acute nonlymphocytic leukemia (ANLL) in second or subsequent remission, who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.

II. Determine the incidence of graft-versus-host disease in this setting.

III. Determine whether contamination of umbilical cord blood with maternal cells is a clinical problem in this setting.

IV. Describe the incidence of leukemic relapse in these patients after UCB transplantation.

V. Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.

VI. Determine specifically whether larger recipients (greater than 40 kg) can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.

PROTOCOL OUTLINE: Patients undergo a back-up bone marrow harvest prior to treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5, followed by melphalan IV on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV on days -3 to -1. If TBI is not allowed, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. On day 0, patients receive umbilical cord blood infusion. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.

Patients are followed indefinitely for survival and late toxicity.

PROJECTED ACCRUAL: A minimum of 48 patients will be accrued into this study within 4 years.

Ages Eligible for Study:  up to  54 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed malignancy including: Pediatric acute lymphocytic leukemia (ALL) in first complete remission with high risk features including presence of t(4;11) or t(9;22), or extreme hyperleukocytosis (initial WBC greater than 500 K/mL), or failure to achieve a complete remission after standard induction therapy; Adult ALL or acute nonlymphoblastic leukemia (ANLL) in first complete remission with t(8;14) translocation or failure to achieve complete remission after standard induction therapy; ALL or ANLL in second or subsequent remission; Chronic myelogenous leukemia in chronic or accelerated phase; Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia; Refractory anemia with excess blasts; Refractory anemia with excess blasts in transformation; Chronic myelomonocytic leukemia; T-lymphoblastic non-Hodgkin's lymphoma in second or subsequent remission; Stage IV neuroblastoma
• Must also meet all the following conditions: No HLA-ABC/DR identical related bone marrow or UCB donor; No 5/6 antigen matched related bone marrow or UCB donor; Condition precludes waiting to search and find a donor in the National Marrow; Donor Registry
• Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project
• No active CNS disease
• Not eligible for COBLT study (Transplantation of Banked Umbilicial Cord Blood Cells for Use in Clinical Research on Transplantation of Umbilical Cord Blood Stem and Progenitor Cells)

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: Under 55 at time of umbilical cord blood transplantation
• Performance status: Zubrod 0-1; Lansky 80-100% Karnofsky 80-100%
• Life expectancy: At least 3 months
• Hematopoietic: Adequate hematologic status at time of back-up bone marrow harvest: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: ALT/AST no greater than 4 times normal; Bilirubin no greater than 2.0 mg/dL
• Renal: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 50 mL/min
• Cardiovascular: Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)
• Pulmonary: FVC and FEV1 at least 60% of predicted for age; For adults: DLCO at least 60% of predicted
• Other: No active infections at time of back-up bone marrow harvest or pretransplant reduction; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative

Florida
      Division of Pediatric Surgery, Jacksonville,  Florida,  32207,  United States
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612,  United States
      Nemours Children's Clinic, Jacksonville,  Florida,  32207,  United States
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States
Illinois
      Rush-Presbyterian-St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
Louisiana
      Children's Hospital of New Orleans, New Orleans,  Louisiana,  70118,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      New York Blood Center, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
Pennsylvania
      St. Christopher's Hospital for Children, Philadelphia,  Pennsylvania,  19134-1095,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
      University of South Carolina School of Medicine, Columbia,  South Carolina,  29203,  United States

Study chairs or principal investigators

Barbara Jean Bambach,  Study Chair,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000066754; RPCI-RP-9801; NCI-G98-1485; DUMC-344-98-2R4
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003661
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08