Phase II Trial of T-Cell Depleted Hematopoietic Stem Cell Transplants (SBA-E-BM) From HLA Compatible Related or Unrelated Donors After a Myeloablative Preparative Regimen of Hyperfractionated TBI, Thiotepa and Cyclophosphamide (TBI/Thio/cy) for Treatment of Patients Less Than or Equal to 18 Years With Lymphohematopoietic Disorders
N/A
18 Years
Both
Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Phase II Trial of T-Cell Depleted Hematopoietic Stem Cell Transplants (SBA-E-BM) From HLA Compatible Related or Unrelated Donors After a Myeloablative Preparative Regimen of Hyperfractionated TBI, Thiotepa and Cyclophosphamide (TBI/Thio/cy) for Treatment of Patients Less Than or Equal to 18 Years With Lymphohematopoietic Disorders
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Minimal transplantation related mortality
Safety Issue:
No
Principal Investigator
Nancy A. Kernan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000069123
NCT ID:
NCT00028730
Start Date:
August 2001
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- recurrent childhood lymphoblastic lymphoma
- chronic phase chronic myelogenous leukemia
- childhood acute myeloid leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- secondary acute myeloid leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- Neoplasms
- Leukemia
- Lymphoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
