Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases
N/A
70 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Trial Information
Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases
OBJECTIVES:
Primary
- Determine the feasibility (i.e., risk of treatment-related mortality during the first 6
months after transplantation) of administering reduced-intensity allogeneic
hematopoietic stem cell transplantation to patients with hematologic cancer or other
diseases.
Secondary
- Determine the response rate (partial and complete response), 6- and 12-month
probabilities of response, and time to progression in patients treated with this
regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated
with this regimen.
- Determine other toxicities of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this
regimen.
- Determine the impact of iron status on overall and disease-free survival.
- Determine the influence of quality of life (at time of transplantation) on overall
survival.
OUTLINE:
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days
-7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and
-3 or melphalan IV over 2 hours on day -3.
- Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors
receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180.
Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched
unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days
-1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral
mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients
also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.
- Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem
cell transplantation or bone marrow transplantation on day 0. Patients receive
filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.
- Lymphocyte infusion: Patients with progressive or stable disease while off
immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions
from the original donor at 8-week intervals beginning on day 180 or 210 .
Quality of life is assessed at baseline.
After completion of study therapy, patients are followed every 3 months for 2 years and then
every 6 months for up to 3 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Inclusion Criteria:
- Histologically confirmed hematological disease, including any of the following:
- Chronic lymphocytic leukemia
- Absolute lymphocytosis > 5,000/µL
- Morphologically mature lymphocytes with < 55% prolymphocytes
- Lymphocyte phenotype with expression of CD19 and CD5
- Absence of CD23 expression allowed provided disease is morphologically
distinguished from mantle cell lymphoma
- Prolymphocytic leukemia
- Absolute lymphocytosis > 5,000/µL
- Morphologically mature lymphocytes with > 55% prolymphocytes
- Non-Hodgkin's or Hodgkin's lymphoma
- Any WHO classification histologic subtype
- Diagnosis by core biopsy allowed provided there is adequate tissue for
diagnosis and immunophenotyping
- Diagnosis by bone marrow biopsy not acceptable for follicular lymphomas
- Multiple myeloma
- Has received ≥ 1 prior treatment regimen
- Has a partial response or greater by the Blade Criteria
- Patients who achieved complete remission are eligible
- Acute myeloid leukemia
- Documented control (i.e., < 10% bone marrow blasts and no circulating
blasts)
- Myelodysplastic syndromes
- Documented disease as defined by WHO or French-American-British Cooperative
group criteria
- Chronic myelogenous leukemia
- Patients with atypical chronic myelogenous leukemia (i.e., absent Philadelphia
chromosome) are eligible
- Polycythemia vera
- Documented disease as defined by WHO criteria (i.e., A1 + A2, and any other
category A, OR A1 + A2, and any 2 category B):
- A1: Total red blood cell mass > 25% above mean normal predicted value
OR hemoglobin > 18.5 g/dL in males, 16.5 g/dL in females (hematocrit ≥
60% in males or ≥ 56% in females)
- A2: No cause of secondary erythrocytosis (absence of familial
erythrocytosis, no elevation of epoetin alfa [EPO] due to hypoxia,
high oxygen affinity hemoglobin, truncated EPO receptor, or
inappropriate ectopic EPO production)
- A3: Splenomegaly
- A4: Clonal genetic abnormality other than the Philadelphia chromosome
- A5: Endogenous erythroid colony formation in vitro
- B: Platelet count > 400,000/mm³, WBC > 12,000/mm³, bone marrow biopsy
with prominent erythroid and megakaryocytic proliferation, and low
serum EPO
- Chronic idiopathic myelofibrosis
- Documented disease as defined by WHO criteria
- Must have a HLA-identical donor, a matched unrelated donor, or a HLA 9/10
related donor meeting the following criteria:
- HLA-identical sibling (6/6)
- Serologic typing for class I (A, B)
- Molecular typing for class II (DRB1)
- 9/10 matched related donor
- High-resolution molecular typing at HLA-A, B, C, DRB1, and DQB1
- Only a single mismatch at one class I or II allele allowed
- 10/10 matched unrelated donor
- Molecular identity at HLA-A, B, C, DRB1, and DQB1 by high-resolution
typing
- Syngeneic donors are not eligible
- Creatinine clearance ≥ 40 mL/min
- Bilirubin ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- DLCO ≥ 40% with no symptomatic pulmonary disease
- LVEF ≥ 30% by cardiac MRI or echocardiogram with no symptomatic cardiac disease
- Fertile patients willing to use effective contraception
Exclusion Criteria:
- Uncontrolled diabetes mellitus
- Active serious infection
- Known hypersensitivity to E. coli-derived products
- Known HIV positivity
- History of another malignancy*, meeting the following criteria:
- Non-skin malignancy or melanoma within the past 5 years
- Concomitant malignancy that has not been curatively treated
- NOTE: *However, cancer survivors who have undergone potentially curative therapy
for a prior malignancy at least 5 years before enrollment and are deemed at low
risk of < 30% for recurrence by their treating physicians is considered
- Pregnant or nursing
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Treatment-related mortality within the first 6 months after transplantation
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
David Hurd, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Wake Forest University Baptist Medical Center
Authority:
United States: Institutional Review Board
Study ID:
CDR0000538185
NCT ID:
NCT00453206
Start Date:
February 2007
Completion Date:
February 2015
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- 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
- adult acute myeloid leukemia in remission
- blastic phase chronic myelogenous leukemia
- primary myelofibrosis
- chronic phase chronic myelogenous leukemia
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- de novo myelodysplastic syndromes
- nodal marginal zone B-cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- previously treated myelodysplastic syndromes
- prolymphocytic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult Burkitt lymphoma
- recurrent adult Hodgkin 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
- refractory chronic lymphocytic leukemia
- refractory multiple myeloma
- relapsing chronic myelogenous leukemia
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- splenic marginal zone lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III adult Burkitt lymphoma
- stage III adult Hodgkin lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III multiple myeloma
- stage III small lymphocytic lymphoma
- stage IV adult Burkitt lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV chronic lymphocytic leukemia
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- polycythemia vera
- stage III chronic lymphocytic leukemia
- recurrent/refractory childhood Hodgkin lymphoma
- stage I childhood Hodgkin lymphoma
- stage II childhood Hodgkin lymphoma
- stage III childhood Hodgkin lymphoma
- stage IV childhood Hodgkin lymphoma
- recurrent childhood anaplastic large cell lymphoma
- stage I childhood anaplastic large cell lymphoma
- stage II childhood anaplastic large cell lymphoma
- stage III childhood anaplastic large cell lymphoma
- stage IV childhood anaplastic large cell lymphoma
- recurrent childhood grade III lymphomatoid granulomatosis
- recurrent childhood large cell lymphoma
- stage I childhood large cell lymphoma
- stage II childhood large cell lymphoma
- stage III childhood large cell lymphoma
- stage IV childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- stage I childhood lymphoblastic lymphoma
- stage II childhood lymphoblastic lymphoma
- stage III childhood lymphoblastic lymphoma
- stage IV childhood lymphoblastic lymphoma
- childhood nasal type extranodal NK/T-cell lymphoma
- recurrent childhood small noncleaved cell lymphoma
- stage I childhood small noncleaved cell lymphoma
- stage II childhood small noncleaved cell lymphoma
- stage III childhood small noncleaved cell lymphoma
- stage IV childhood small noncleaved cell lymphoma
- Neoplasms
- Hematologic Diseases
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Lymphoma, Large-Cell, Anaplastic
Name | Location |
|---|---|
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
