RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and 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: Phase II trial to study the effectiveness of total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplantation in treating children who have hematologic cancer.

Condition	Treatment or Intervention	Phase
acute leukemia childhood large cell lymphoma childhood lymphoblastic lymphoma childhood small noncleaved cell lymphoma chronic leukemia myelodysplastic and myeloproliferative disease	Drug: anti-thymocyte globulin  Drug: cyclophosphamide  Drug: filgrastim  Drug: fludarabine  Drug: thiotepa  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: non-specific immune-modulator therapy  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide followed by T-cell-depleted allogeneic bone marrow transplantation in children with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, or myelodysplastic syndromes.
• Correlate the progenitor cell dose and dose of clonable T cells with the incidence and quality of engraftment, extent of chimerism, incidence and severity of acute and chronic graft-versus-host disease, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival at 2 years in patients treated with this regimen.

OUTLINE: Patients undergo total body irradiation three times daily on days -9 to -7 and twice on day -6. Patients receive thiotepa IV over 4 hours on days -5 and -4 and cyclophosphamide IV over 30 minutes on days -3 and -2. Patients who cannot receive cyclophosphamide, due to prior hemorrhagic cystitis or exposure to high-dose cyclophosphamide or ifosfamide, receive fludarabine IV over 30 minutes on days -5 to -1. Patients planning to receive family member HLA-mismatched or unrelated bone marrow transplantation receive horse anti-thymocyte globulin IV once daily on days -5 and -4. Patients undergo allogeneic T-cell-depleted bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) IV every 12 hours beginning on day 7 and continuing until blood counts recover.

Patients are followed every 2-4 weeks for the first 100 days post-transplantation, every 6 weeks for 6 months, every 3 months for 1 year, and then every 3-6 months until 2 years post-transplantation.

PROJECTED ACCRUAL: A total of 50 patients (25 with HLA 6/6 antigen-matched related donors and 25 with HLA 5/6 antigen-matched related donors or HLA 5/6 or 6/6 antigen-matched unrelated donors) will be accrued for this study within 3 years.

Ages Eligible for Study:  up to  18 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• One of the following diagnoses:
• Histologically confirmed good-risk acute myeloid leukemia (AML) in first remission with an HLA-compatible related donor
• Ineligible for unrelated bone marrow transplantation unless failed first-line induction chemotherapy or have molecular evidence of disease at time of transplantation
• Histologically confirmed high-risk AML in first remission
• High risk defined by cytogenetics, biphenotypic and undifferentiated leukemia phenotype, secondary AML, or AML after myelodysplastic syndromes (MDS)
• Eligible for related or unrelated donor transplantation
• Histologically confirmed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) in first remission with high risk for relapse or in second or third remission
• High risk for relapse defined by hypodiploidy, pseudodiploidy with translocations t(9;22) or infant t(4;11), or failure to achieve remission after four weeks of induction therapy
• Eligible for related or unrelated donor transplantation
• Histologically confirmed chronic myelogenous leukemia (CML) in at least first chronic phase or acceleration with an HLA-compatible related donor
• Histologically confirmed CML in first chronic phase if failed conventional therapy or in at least second chronic phase or acceleration with an HLA-compatible unrelated donor
• Histologically confirmed non-Hodgkin's lymphoma beyond first complete remission or primary induction failure and tumors that are chemosensitive defined as at least 50% reduction in mass size
• Eligible for related or unrelated donor transplantation
• Histologically confirmed MDS with intermediate or high-risk disease defined by International Prognostic Scoring System and paroxysmal nocturnal hematuria
• Eligible for related or unrelated donor transplantation
• Treatment-related MDS or leukemia allowed if primary malignancy (e.g., neuroblastoma or Ewing's sarcoma) at low risk of recurrence
• No AML, ALL, or LL in relapse or greater than third remission
• No CML in blast crisis defined as more than 30% blasts plus promyelocytes
• No active CNS involvement
• History of leukemia cutis allowed
• HLA compatible donor available
• 5/6 or 6/6 HLA antigen matched related or unrelated

PATIENT CHARACTERISTICS: Age:

• 18 and under

Performance status:

• Karnofsky 70-100% OR
• Lansky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN (unless liver involvement is present)

Renal:

• Creatinine normal OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• LVEF at least 50% at rest (if less than 50% at rest, must increase with exercise)

Pulmonary:

• Asymptomatic with no prior risk features OR
• DLCO greater than 40% predicted (corrected for hemoglobin) if symptomatic

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV I/II negative
• No uncontrolled viral, bacterial, or fungal infection
• No known hypersensitivity to bovine proteins

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characterisitics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy that would preclude total body irradiation dose

Surgery:

• Not specified

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Nancy A. Kernan, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000069123; MSKCC-01105; NCI-H01-0083; NCT00028730
Record last reviewed:  December 2002
Last Updated:  December 6, 2004
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028730
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08