A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders
N/A
N/A
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases, Precancerous/Nonmalignant Condition
Trial Information
A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders
OBJECTIVES:
Primary
- To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the
primary criterion, in patients with advanced hematologic malignancies or other
disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from
matched unrelated donors.
- To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in
patients undergoing allogeneic PBSC transplantation from matched unrelated donors.
Secondary
- To evaluate the impact of HLA class I and class II allele-matching on the incidence of
GVHD and on the survival outcome of these patients.
- To evaluate overall survival, disease-free survival, and relapse in these patients.
OUTLINE: Patients are stratified according to type of conditioning regimen (myeloablative vs
reduced-intensity myeloablative). Patients are assigned to a conditioning regimen according
to diagnosis, age, disease status, prior radiotherapy, and prior autologous stem cell
transplantation.
- Conditioning regimen:
- Regimen I: Patients undergo total body irradiation (TBI) on days -7 to -4 and
receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive
cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
- Regimen II: Patients receive busulfan IV over 2 hours once on day -8 and then
every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days
-3 and -2.
- Regimen III: Patients undergo TBI on days -7 to -4 and receive etoposide IV on day
-3.
- Regimen IV: Patients receive fludarabine phosphate IV over 30 minutes on days -7
to -3 and melphalan IV on day -2.
- Regimen V: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to
-2 and undergo TBI on day 0.
- Regimen VI: Patients receive busulfan IV over 3 hours and fludarabine phosphate IV
over 30 minutes on days -5 to -2.
- Allogeneic peripheral blood stem cell (PBSC) transplantation: All patients undergo
allogeneic PBSC transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive one of the following
GVHD prophylaxis regimens:
- Regimen A: Patients receive tacrolimus IV or orally on days -1 to 180 and
methotrexate IV on days 1, 3, 6, and 11.
- Regimen B: Patients receive cyclosporine IV or orally twice daily on days -1 to
180, mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-27, and
methotrexate IV on days 1, 3, and 6.
- Regimen C: Patients receive tacrolimus IV continuously or orally, and oral
sirolimus beginning on day -3. Patients also receive methotrexate IV on days 1, 3,
and 6.
After completion of study therapy, patients are followed periodically.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of one of the following:
- Acute lymphocytic leukemia (ALL), meeting one of the following criteria:
- In first relapse or beyond
- High-risk ALL, defined by any of the following:
- Hypoploidy (≤ 44 chromosomes)
- Pseudodiploidy with translocations or molecular evidence of t(9;22),
11q23, or t(8;14), excluding B-cell ALL
- Elevated WBC at presentation (WBC > 20,000/mm³ [for patients > 18
years of age]; WBC > 200,000/mm³ [for patients 12-18 years of age])
- Acute myeloid leukemia (AML), meeting one of the following criteria:
- In first complete remission
- Failed to achieve remission
- In first relapse or beyond
- Secondary AML (> 30% blasts in marrow aspirate)
- Should receive induction chemotherapy to obtain remission, if
possible, before transplant
- Chronic myelogenous leukemia, meeting one of the following criteria:
- In first or second chronic phase or accelerated phase
- In blast crisis, defined as > 30% promyelocytes plus blasts in the bone
marrow
- Myelodysplastic syndromes, including any of the following:
- Refractory anemia with excess blasts (RAEB)
- Chronic myelomonocytic leukemia
- RAEB in transformation
- Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma,
or multiple myeloma
- Received and failed front-line therapy, high-dose therapy and autologous
stem cell transplantation, or salvage therapy
- Myeloproliferative disorders/myelofibrosis may be allowed on a case by case
basis
- Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other
hematologic disorder requiring transplantation
- Patients > 55 years of age with hematologic diseases treatable by allogeneic stem
cell transplantation who are not eligible for IRB 99190 are eligible
- No uncontrolled CNS involvement of disease
- No matched (6/6) related donor available
- HLA-identical unrelated donor available
- HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1
alleles by DNA typing for both class I and class II antigens
- Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no
alternative donors
- Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch
for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in
patients ≤ 35 years of age requiring urgent transplant
PATIENT CHARACTERISTICS:
- Karnofsky performance status 50-100%
- Life expectancy > 8 weeks
- LVEF ≥ 45% at rest
- AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease)
- Total bilirubin < 1.5 times normal (unless liver function abnormality is due to
underlying disease)
- Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min
- DLCO ≥ 40% of predicted (corrected for hemoglobin)
- No coexisting medical problem that would significantly increase the risk of the
transplant procedure
- HIV negative
- Not pregnant
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Neutrophil and platelet engraftment
Safety Issue:
No
Principal Investigator
Auayporn P. Nademanee, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Federal Government
Study ID:
01089
NCT ID:
NCT00544115
Start Date:
September 2001
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Graft Versus Host Disease
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Diseases
- Precancerous/Nonmalignant Condition
- graft versus host disease
- recurrent adult acute lymphoblastic leukemia
- recurrent childhood acute lymphoblastic leukemia
- untreated adult acute lymphoblastic leukemia
- untreated childhood acute lymphoblastic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- atypical chronic myeloid leukemia
- chronic myelomonocytic leukemia
- juvenile myelomonocytic leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- adult acute myeloid leukemia in remission
- childhood acute myeloid leukemia in remission
- secondary acute myeloid leukemia
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- childhood chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- chronic eosinophilic leukemia
- chronic idiopathic myelofibrosis
- chronic neutrophilic leukemia
- essential thrombocythemia
- polycythemia vera
- Waldenstrom macroglobulinemia
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- splenic marginal zone lymphoma
- recurrent childhood grade III lymphomatoid granulomatosis
- childhood nasal type extranodal NK/T-cell lymphoma
- recurrent childhood large cell lymphoma
- childhood diffuse large cell lymphoma
- childhood immunoblastic large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- Burkitt lymphoma
- recurrent childhood small noncleaved cell lymphoma
- anaplastic large cell lymphoma
- angioimmunoblastic T-cell lymphoma
- recurrent adult T-cell leukemia/lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- adult nasal type extranodal NK/T-cell lymphoma
- recurrent adult Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- refractory chronic lymphocytic leukemia
- refractory multiple myeloma
- stage III multiple myeloma
- aplastic anemia
- paroxysmal nocturnal hemoglobinuria
- adult acute lymphoblastic leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- stage II multiple myeloma
- Neoplasms
- Graft vs Host Disease
- Hematologic Diseases
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Precancerous Conditions
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
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