Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed By T Cell Add-Back For Hematological Malignancies - Effect Of Irradiated Donor Lymphocytes On Chimerism
10 Years
55 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed By T Cell Add-Back For Hematological Malignancies - Effect Of Irradiated Donor Lymphocytes On Chimerism
OBJECTIVES:
- Determine the effect of irradiated donor T-cell infusion on donor T-cell chimerism 6
weeks after hematopoietic stem cell transplantation in patients with hematologic
malignancies.
- Determine the infusional toxic effects of irradiated donor lymphocytes in these
patients.
- Determine the risk of acute and chronic graft-versus-host disease from donor lymphocyte
infusions on day 45 and day 100 posttransplantation in HLA 6/6 matched transplantations
from a related donor in these patients.
- Determine disease-free survival, cytomegalovirus reactivation, and relapse in patients
treated with this regimen.
- Determine transplant-related mortality and death from all causes in patients treated
with this regimen.
OUTLINE:
- Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4
and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo total body
irradiation on days -7 to -4.
- Pretransplantation irradiated donor lymphocyte infusion (DLI): Patients receive
irradiated DLI on day -4.
- Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day
0.
- Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine on days
44-120.
- Posttransplantation DLI: Patients receive DLI on days 45 and 100. Patients with chronic
myelogenous leukemia in chronic phase who are polymerase chain reaction negative for
bcr/abl receive DLI on day 45 only.
Patients are followed at 3, 6, and 12 months and then annually thereafter.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of any of the following hematologic malignancies:
- Chronic myelogenous leukemia (CML) in chronic phase meeting 1 of the following
criteria:
- Under 41 years of age with no prior imatinib mesylate therapy
- 10 to 55 years of age and failed prior imatinib mesylate therapy
- 41 to 55 years of age for whom imatinib mesylate is not the treatment of
choice
- CML in accelerated phase or blast transformation
- Acute lymphoblastic leukemia meeting any of the following criteria:
- Over 18 years of age and in first remission with high-risk features (e.g.,
WBC greater than 100,000/mm^3, karyotypes t[9;22], t[4], t[19], t[11], and
biphenotypic leukemia)
- Second or subsequent remission
- Primary induction failure
- Partially responding or untreated relapse
- Acute myeloid leukemia meeting any of the following criteria:
- First remission, except with good-risk karyotypes (e.g., M3 t[15;17], M4E0
inv[16], t[8;21])
- Second or subsequent remission
- Primary induction failure
- Resistant relapse
- Myelodysplastic syndromes of any of the following types:
- Refractory anemia (RA) with transfusion dependence
- RA with excess blasts
- In transformation to acute leukemia
- Chronic myelomonocytic leukemia
- Myeloproliferative disorders in transformation to acute leukemia, of any of the
following types:
- Myelofibrosis
- Polycythemia vera
- Essential thrombocythemia
- Chronic lymphocytic leukemia that is refractory to fludarabine with 1 of the
following:
- Bulky progressive disease
- Thrombocytopenia (WBC no greater than 100,000/mm^3)*
- Anemia (hemoglobin no greater than 10 g/dL)* NOTE: *Not due to recent
chemotherapy
- Non-Hodgkin's lymphoma, including mantle cell lymphoma, relapsing or refractory
to current chemotherapy and monoclonal antibody therapy and unsuitable for
autologous stem cell transplantation
- Availability of a HLA-identical (6/6) family donor
PATIENT CHARACTERISTICS:
Age
- 10 to 55
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin no greater than 4 mg/dL
- Transaminases no greater than 3 times upper limit of normal
Renal
- Creatinine no greater than 3 mg/dL
Cardiovascular
- LVEF at least 40% of predicted
Pulmonary
- DLCO at least 60% of predicted
Other
- Not pregnant
- Negative pregnancy test
- HIV negative
- No severe psychiatric illness or mental deficiency that would preclude giving
informed consent or complying with study treatment
- No major illness or organ dysfunction that would preclude transplantation
- No other prior malignancy except basal cell or squamous cell skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- See Disease Characteristics
- No prior continuous busulfan for more than 6 months duration
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Austin J. Barrett, MD, FRCP
Investigator Role:
Study Chair
Investigator Affiliation:
NHLBI - Bone Marrow Transplantation Unit
Authority:
United States: Federal Government
Study ID:
CDR0000315460
NCT ID:
NCT00066300
Start Date:
May 2003
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- primary myelofibrosis
- polycythemia vera
- essential thrombocythemia
- adult acute lymphoblastic leukemia in remission
- recurrent adult acute lymphoblastic leukemia
- adult acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- refractory chronic lymphocytic leukemia
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- chronic myelomonocytic leukemia
- refractory anemia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood acute myeloid leukemia
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- de novo myelodysplastic syndromes
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- atypical chronic myeloid leukemia, BCR-ABL1 negative
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- childhood myelodysplastic syndromes
- Neoplasms
- Leukemia
- Lymphoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center | Bethesda, Maryland 20892-1182 |
