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Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases


Phase 2
N/A
70 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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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 CenterWinston-Salem, North Carolina  27157-1096