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Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen


Phase 2
6 Months
45 Years
Open (Enrolling)
Both
Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Phase Chronic Myelogenous Leukemia, Contiguous Stage II Adult Burkitt Lymphoma, Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Contiguous Stage II Adult Lymphoblastic Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Mantle Cell Lymphoma, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, 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 Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Prolymphocytic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood 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 Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Chronic Lymphocytic Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, Stage I Adult Burkitt Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Mixed Cell Lymphoma, Stage I Adult Immunoblastic Large Cell Lymphoma, Stage I Adult Lymphoblastic Lymphoma, Stage I Childhood Anaplastic Large Cell Lymphoma, Stage I Childhood Large Cell Lymphoma, Stage I Childhood Lymphoblastic Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle Cell Lymphoma, Stage II Childhood Anaplastic Large Cell Lymphoma, Stage II Childhood Large Cell Lymphoma, Stage II Childhood Lymphoblastic Lymphoma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Childhood Anaplastic Large Cell Lymphoma, Stage III Childhood Large Cell Lymphoma, Stage III Childhood Lymphoblastic Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Childhood Anaplastic Large Cell Lymphoma, Stage IV Childhood Large Cell Lymphoma, Stage IV Childhood Lymphoblastic Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Waldenström Macroglobulinemia

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Trial Information

Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen


PRIMARY OBJECTIVES:

I. To determine the one year survival of patients undergoing umbilical cord blood
transplantation (UCBT) after a myeloablative preparative regimen consisting of
cyclophosphamide (CY), fludarabine (FLU), and fractionated total body irradiation (TBI).

SECONDARY OBJECTIVES:

I. Incidence of transplant-related mortality (TRM) at 6 months.

II. Chimerism at multiple time points.

III. Incidence of neutrophil engraftment at Day 42.

IV. Incidence of platelet engraftment 6 months.

V. Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at Day
100.

VI. Incidence of chronic GVHD at Day 100, 1 year and 2 years.

VII. Incidence of clinically significant infections at 6 months, 1 year and 2 years.

VIII. Incidence of disease free survival at 1 and 2 years.

IX. Incidence of relapse at 1 and 2 years.

OUTLINE:

Patients receive myeloablative conditioning comprising FLU intravenously (IV) over 1 hour on
days -8 to -6, CY IV on days -7 and -6, and undergo TBI twice daily on days -4 to -1.
Patients then undergo single- or double-unit UCBT on day 0.

Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12
hours, then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day
101. Patients also receive mycophenolate mofetil IV every 8 hours on days -3 to 5 and then
mycophenolate mofetil PO (if tolerated) on days 6-30. Mycophenolate mofetil is discontinued
on day 30 or 7 days after engraftment if there is no acute GVHD.

After completion of study treatment, patients are followed up at 6 months, 1 year, and 2
years.


Inclusion Criteria:



- GRAFT CRITERIA:

- UCB units will be selected according to current umbilical cord blood graft
selection algorithm; one or 2 UCB units may be used to achieve the required cell
dose

- The UCB graft is matched at 4-6 human leukocyte antigen (HLA)-A, B, DRB1
antigens with the recipient; this may include 0-2 antigen mismatches at the A or
B or DRB1 loci; unit selection based on cryopreserved nucleated cell dose and
HLA-A,B, DRB1 using intermediate resolution A, B antigen and DRB1 allele typing

- If 2 UCB units are required to reach the target cell dose, each unit must be a
4-6 antigen match to the recipient

- Acute myeloid leukemia (AML):

- High risk first complete remission (CR1) as evidenced by preceding
myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5
or 7), or high risk as defined by referring institution treatment protocol, >= 2
cycles to obtain complete response (CR), erythroblastic or megakaryocytic
leukemia; >= second complete remission (CR2)

- All patients must be in CR as defined by hematologic recovery and < 5% blasts by
morphology within the bone marrow and a cellularity of >= 15%

- Patients in which adequate marrow/biopsy specimens cannot be obtained to
determine remission status by morphologic assessment, but have fulfilled
criteria of remission by flow cytometry, recovery of peripheral blood counts
with no circulating blasts, and/or normal cytogenetics (if applicable) may still
be eligible; reasonable attempts must be made to obtain an adequate specimen for
morphologic assessment, including possible repeat procedures

- Very high risk pediatric/young adult patients with AML: Patients < 25 years, however,
are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or
more cycles of chemotherapy; this group of patients will be analyzed separately

- Acute Lymphoblastic Leukemia (ALL):

- High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or
other mixed lineage leukemia (MLL) rearrangements, hypodiploid]

- Greater than 1 cycle to obtain CR

- >= CR2

- All patients must be in CR as defined by hematologic recovery and < 5% blasts by
morphology within the bone marrow and a cellularity of >= 15%

- Patients in which adequate marrow/biopsy specimens cannot be obtained to
determine remission status by morphologic assessment, but have fulfilled
criteria of remission by flow cytometry, recovery of peripheral blood counts
with no circulating blasts, and/or normal cytogenetics (if applicable) may still
be eligible; reasonable attempts must be made to obtain an adequate specimen for
morphologic assessment, including possible repeat procedures

- Chronic myelogenous leukemia (CML) excluding refractory blast crisis; to be eligible
in first chronic phase (CP1) patient must have failed or be intolerant to imatinib
mesylate

- Advanced myelofibrosis

- Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) Int-2 or High
risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation
[RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics;
blasts must be < 10% by a representative bone marrow aspirate morphology

- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial
therapy if stage III/IV in first partial response (PR1) or after progression if stage
I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR

- Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone
B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have
progressed after at least two different prior therapies; patients with bulky disease
(nodal mass greater than 5 cm) should be considered for debulking chemotherapy before
transplant; these patients must be presented at primary care center (PCC) prior to
enrollment, given potential competing eligibility on autotransplant protocols

- Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >=
CR1 or >= PR1

- Large cell Non-Hodgkin lymphoma (NHL):

- Patients in CR2/second partial response (PR2) with initial short remission (< 6
months) are eligible

- These patients must be presented at PCC prior to enrollment, given potential
competing eligibility on autotransplant protocols

- Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first
response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be
considered for this protocol after initial therapy

- Performance status score: Karnofsky (for adults) >= 70% or Lansky (for children) >=
50%

- Creatinine < 2.0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for
children)

- Patients with clinical or laboratory evidence of liver disease will be evaluated for
the cause of liver disease, its clinical severity in terms of liver function,
histology, and the degree of portal hypertension; patients with fulminant liver
failure, cirrhosis with evidence of portal hypertension or bridging fibrosis,
alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices,
hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by
prolongation of the prothrombin time, ascites related to portal hypertension,
bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total
serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded

- Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal

- Left ventricular ejection fraction > 45% or shortening fraction > 26%

Exclusion Criteria:

- Uncontrolled viral or bacterial infection at the time of study enrollment

- Active or recent (prior 6 month) invasive fungal infection without interdisciplinary
(ID) consult and approval

- History of human immunodeficiency virus (HIV) infection

- Pregnant or breastfeeding

- Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease
after > 2 salvage regimens)

- Prior myeloablative transplant containing full dose TBI (greater than 8 Gray [Gy])

- Any prior myeloablative transplant within the last 6 months

- Extensive prior therapy including > 12 months alkylator therapy or > 6 months
alkylator therapy with extensive radiation

- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar),
as part of their salvage therapy are not eligible for myeloablative umbilical cord
blood transplant

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

A non-statistical comparison with historical controls will be made.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Colleen Delaney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

2010.00

NCT ID:

NCT00719888

Start Date:

November 2005

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • 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)
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Immunoblastic Large Cell Lymphoma
  • Childhood Myelodysplastic Syndromes
  • Childhood Nasal Type Extranodal NK/T-cell Lymphoma
  • Chronic Phase Chronic Myelogenous Leukemia
  • Contiguous Stage II Adult Burkitt Lymphoma
  • Contiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  • Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  • Contiguous Stage II Adult Lymphoblastic Lymphoma
  • Contiguous Stage II Grade 3 Follicular Lymphoma
  • Contiguous Stage II Mantle Cell Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • 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 Immunoblastic Large Cell Lymphoma
  • Noncontiguous Stage II Adult Lymphoblastic Lymphoma
  • Noncontiguous Stage II Grade 3 Follicular Lymphoma
  • Noncontiguous Stage II Mantle Cell Lymphoma
  • Previously Treated Myelodysplastic Syndromes
  • Primary Myelofibrosis
  • Prolymphocytic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Childhood Anaplastic Large Cell Lymphoma
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood 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 Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Multiple Myeloma
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Splenic Marginal Zone Lymphoma
  • Stage I Adult Burkitt Lymphoma
  • Stage I Adult Diffuse Large Cell Lymphoma
  • Stage I Adult Diffuse Mixed Cell Lymphoma
  • Stage I Adult Immunoblastic Large Cell Lymphoma
  • Stage I Adult Lymphoblastic Lymphoma
  • Stage I Childhood Anaplastic Large Cell Lymphoma
  • Stage I Childhood Large Cell Lymphoma
  • Stage I Childhood Lymphoblastic Lymphoma
  • Stage I Grade 3 Follicular Lymphoma
  • Stage I Mantle Cell Lymphoma
  • Stage II Childhood Anaplastic Large Cell Lymphoma
  • Stage II Childhood Large Cell Lymphoma
  • Stage II Childhood Lymphoblastic Lymphoma
  • Stage III Adult Burkitt Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Adult Diffuse Mixed Cell Lymphoma
  • Stage III Adult Immunoblastic Large Cell Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Childhood Anaplastic Large Cell Lymphoma
  • Stage III Childhood Large Cell Lymphoma
  • Stage III Childhood Lymphoblastic Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Childhood Anaplastic Large Cell Lymphoma
  • Stage IV Childhood Large Cell Lymphoma
  • Stage IV Childhood Lymphoblastic Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Waldenström Macroglobulinemia
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Burkitt Lymphoma
  • Hematologic Diseases
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Leukemia, Prolymphocytic
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, T-Cell
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Anemia, Aplastic
  • Lymphoma, Mantle-Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
VA Puget Sound Health Care SystemSeattle, Washington  98101
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045