RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. PURPOSE: Randomized phase II/III trial to compare the effectiveness of conventional bone marrow transplantation with T cell-depleted bone marrow transplantation in treating patients who have leukemia, myelodysplasia, or lymphoblastic lymphoma.

Condition	Treatment or Intervention	Phase
Lymphoma Leukemia	Drug: cyclophosphamide  Drug: cyclosporine  Drug: cytarabine  Drug: filgrastim  Drug: methotrexate  Drug: methylprednisolone	Phase II Phase III

Further Study Details: 

OBJECTIVES: I. Compare the disease free survival of patients with leukemia, myelodysplasia, or lymphoblastic lymphoma after treatment with conventional (non-T cell depleted) or T cell depleted unrelated donor bone marrow transplantation. II. Compare the incidence of primary and secondary graft failure, acute and chronic graft-vs-host disease, complications (infection, veno-occlusive disease, interstitial pneumonitis), and relapse in these patients after these treatments. III. Compare the incidence of other malignancies, lymphoproliferative disorders, and post-transplant myelodysplasia in these patients after these treatments.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients will be stratified according to institution. Patients are assigned to one of two treatment arms, one with conventional bone marrow transplantation (arm I) and one with T cell depletion of the bone marrow (arm II). Arm I: Patients receive cyclophosphamide on days -6 and -5. Total body irradiation (TBI) is administered on days -4 to 0, although this order may be reversed. Males with ALL receive a testicular boost of radiation therapy. Bone marrow is infused on day 0. Patients receive cyclosporine beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Arm II: T cell depletion is conducted by 2 different methods, according to the institution, and treatment varies depending on the method used. Method I is by T10B9 depletion and Method II is by counterflow elutriation depletion. Method I: Depending on the institution, some patients receive TBI on days -9 to -7 (before chemotherapy) (Course I) and some receive TBI on days -3 to -1 (after chemotherapy) (Course II). Course I also includes cytarabine IV on days -5 to -3, cyclophosphamide IV on days -2 and -1, and methylprednisolone IV on days -2 to 0 and 5-18. Bone marrow infusion is administered on day 0. Cyclosporine begins on day -1. Course II includes cytarabine IV on days -7 to -4 and cyclophosphamide on days -6 to -5. Methylprednisolone IV is administered on days -2 to 0 and 5-18. Bone marrow infusion is administered on day 0. Cyclosporine begins on day 0. Method II: Preparative therapy varies according to the disease category. Acute lymphoblastic leukemia: Patients undergo TBI on days -7 to -4. Males receive testicular boost on day -7, and all receive electron boost to anterior and posterior chest wall on days -5 and -4. Cyclophosphamide IV is administered on days -3 and -2. Bone marrow infusion is administered on day 0. Acute nonlymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome: Patients receive cyclophosphamide IV on days -7 and -6, followed by TBI on days -4 to -1. Bone marrow infusion is administered on day 0. Patients receive methylprednisolone IV every 12 hr on days -2,-1, and 5-19. Cyclosporine is administered from day -3 to day 180. All patients on both arms receive filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning on day 7 post-transplant. Patients are followed weekly for the first 14 weeks, at day 100, every 6 months for 2 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 560 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  up to  55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically confirmed acute myeloid leukemia; Not in first complete remission with translocations t(8;21) unless failed first line induction therapy; Not in first complete remission with translocations t(15;17) or 16q abnormality unless: Failed first line induction therapy OR Molecular evidence of disease
• Pathologically confirmed acute lymphoblastic lymphoma (ALL); Not in first complete remission OR High risk ALL in first complete remission defined as: Hypodiploidy OR Pseudodiploidy with translocations t(9,22), t(4;11), or t(8;14) OR Elevated WBC at presentation; Greater than 100,000/mm3 if 6-12 months old; Greater than 50,000/mm3 if 10-20 years old; Greater than 20,000/mm3 if 21 or over OR Failed to achieve complete remission after 4 weeks of induction therapy
• Pathologically confirmed chronic myelogenous leukemia (CML) not in blast crisis
• Pathologically confirmed undifferentiated leukemia or biphenotypic leukemia
• Pathologically confirmed juvenile CML with or without either 7q- or infantile monosomy 7; Leukocytosis with absolute monocytosis greater than 450 microliters AND Immature myeloid cells in peripheral blood circulation Less than 25% marrow blasts
• Myelodysplastic syndromes: Refractory anemia (RA) RA with ringed sideroblasts RA with excess blasts (RAEB); RAEB in transformation; Chronic myelomonocytic leukemia
• Pathologically confirmed stage IV lymphoblastic lymphoma
• No active CNS or skin leukemic involvement
• No consenting suitably HLA-matched related donor available
• Consenting unrelated donor available

--Prior/Concurrent Therapy--

• Biologic therapy: No prior autologous or allogeneic bone marrow transplant
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: No concurrent mediastinal radiation; No prior radiation therapy that would preclude total body irradiation
• Surgery: Not specified

--Patient Characteristics--

• Age: 55 and under
• Performance status: Karnofsky 70-100% OR Lansky 60-100%
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Bilirubin less than 2.5 mg/dL; SGOT less than 3 times upper limit of normal
• Renal: Creatinine within normal range OR Creatinine clearance greater than 60 mL/min
• Cardiovascular: Asymptomatic OR Left ventricular ejection fraction at rest greater than 40% and improves with exercise
• Pulmonary: Asymptomatic OR DLCO greater than 45%
• Other: Not pregnant or lactating; HIV negative; No uncontrolled viral, bacterial, or fungal infection

California
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
Minnesota
      University of Minnesota Medical School, Minneapolis,  Minnesota,  55455,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
North Carolina
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States
Pennsylvania
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
South Carolina
      University of South Carolina School of Medicine, Columbia,  South Carolina,  29203,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
Virginia
      Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States

Study chairs or principal investigators

Lee Ann Jensen,  Study Chair,  Massey Cancer Center   

Study ID Numbers:  CDR0000066016; MCV-CCHR-9504-2X; NCI-G98-1388; DUMC-75951
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00003187
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08