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

Phase 2
55 Years
Open (Enrolling)
Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Myelofibrosis, MDS, Refractory Anemia, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Multiple Myeloma, Non-Hodgkin's Lymphoma, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

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



- Determine the 1-year survival of patients undergoing unrelated umbilical cord blood
transplantation (UCBT) for hematologic malignancies treated with myeloablative
preparative regimen comprising fludarabine, cyclophosphamide, and fractionated
total-body irradiation.


- Determine the incidence of transplant-related mortality at 6 months after UCBT.

- Evaluate the pattern of chimerism after double UCBT.

- Determine the incidence of neutrophil engraftment at day 42 after UCBT.

- Determine the incidence of platelet engraftment at 6 months after UCBT.

- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease
(GVHD) at day 100 after UCBT.

- Determine the incidence of chronic GVHD at 1 year after UCBT.

- Determine the disease-free survival at 1 and 2 years after UCBT.

- Determine the incidence of relapse at 1 year after UCBT.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

- Preparative Regimen: Patients receive fludarabine IV over 1 hour on days -8 to -6 and
cyclophosphamide IV on days -7 and -6. Patients also undergo total-body irradiation
twice daily on days -4 to -1.

- Umbilical Cord Blood Transplantation (UCBT): Patients undergo 1 or 2 units of UCBT on
day 0. Patients receive filgrastim (G-CSF) IV once daily beginning on day 1 and
continuing until blood counts recover.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
hours 2 or 3 times daily beginning on day -3 and continuing until day 100 followed by a
taper until day 180. Patients also receive mycophenolate mofetil IV or orally 2 or 3
times a day beginning on day -3 and continuing until day 30 or 7 days after engraftment
in the absence of acute GVHD.

After completion of study treatment, patients are followed periodically for at least 5

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Inclusion Criteria:

- Graft Criteria

- The unrelated cord blood donor(s) must be 4-6/6 HLA-A, B, DRB1 matched with the
recipient (HLA matching using molecular techniques: A and B to antigen level
resolution and DR to allele level resolution).

- No existing HLA-identical related donor is available.

- Suitable UCB units available according to Umbilical Cord Blood Graft (UCB)
selection algorithm. The UCB graft may consist of one or two UCB units.

- Age and Disease Criteria

- Patients aged ≤ 55 years must have a hematological malignancy as described

- Acute myeloid leukemia (AML): high risk CR1 (as evidenced by preceding
myelodysplastic syndrome [MDS], high risk cytogenetics, ≥ 2 cycles to obtain
complete remission [CR], erythroblastic or megakaryocytic leukemia; CR2+. All
patients must be in CR as defined by hematological recovery, AND <5% blasts by
light microscopy within the bone marrow with a cellularity of ≥15%.

- Very high risk pediatric patients with AML. Patients <21 years, however, are
eligible with (M2 marrow) with < or = 25% blasts in marrow after having failed
one or more cycles of chemotherapy. This group of patients will be analyzed

- Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or
other MLL rearrangements] hypodiploidy, or IKZF1 abnormalities), DNA index <
0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD).
Patients in CR2+ are eligible. All patients must be in CR as defined by
hematological recovery, AND <5% blasts by light microscopy within the bone
marrow with a cellularity of ≥15%.

- Very high risk pediatric patients with ALL. patients <21 years are also
considered high risk CR1 if they had M2 or M3 marrow at day 42 from the
initiation of induction or M3 marrow at the end of induction. They are eligible
once they achieved a complete remission

- 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.

- Plasma Cell leukemia after initial therapy, who achieved at least a partial

- Advanced myelofibrosis

- Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory
anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10%
by a representative bone marrow aspirate morphology.

- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
B-cell lymphoma or follicular lymphoma are eligible if there was disease
progression/relapse within 12 of achieving a partial or complete remission.
Patients who had remissions lasting > 12 months, are eligible after at least two
prior therapies. Patients with bulky disease (nodal mass greater than 5 cm)
should be considered for debulking chemotherapy before transplant.

- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are
eligible after initial therapy in CR1+ or PR1+.

- Large cell NHL > CR2/> PR2. Patients in CR2/PR2 with initial short remission (<6
months) are eligible.

- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after
initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II <
1 year.

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

- Organ function and Performance Status Criteria

- Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50%
(pediatrics) and have acceptable organ function defined as:

- Renal: creatinine < or = 2.0 (adults) or creatinine clearance > 40 ml/min

- Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase
(AST/ALT), Alkaline phosphatase (ALP) < or = 5 x upper limit of normal

- Pulmonary function: Diffusion capacity corrected (DLCOcorr) > 50% normal

- Cardiac: left ventricular ejection fraction > or = 45%.

- Voluntary written informed consent before performance of any study-related
procedure not part of normal medical care.

Exclusion Criteria

- Active infection at time of transplantation (including active infection with
Aspergillus or other mold within 30 days.)

- History of human immunodeficiency virus (HIV) infection

- Pregnant or breast feeding. The agents used in this study may be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk All
females of childbearing potential must have a blood test or urine study within 2
weeks prior to registration to rule out pregnancy.

- Chemotherapy refractory large cell and high grade NHL (ie progressive disease after >
2 salvage regimens)

- If < or = 18 years old, prior myeloablative transplant within the last 6 months. If
>18 years old prior myeloablative allotransplant or autologous transplant

- 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 tostumomab (Bexxar),
as part of their salvage therapy are not eligible for myeloablative umbilical cord
blood transplant.

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Outcome Description:

Number of patients alive at 1 year after transplant.

Outcome Time Frame:

at 1 year

Safety Issue:


Principal Investigator

Claudio G. Brunstein, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

July 2005

Completion Date:

August 2014

Related Keywords:

  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Myelofibrosis
  • MDS
  • Refractory Anemia
  • Chronic Lymphocytic Leukemia
  • Prolymphocytic Leukemia
  • Multiple Myeloma
  • Non-Hodgkin's Lymphoma
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • blastic phase chronic myelogenous leukemia
  • primary myelofibrosis
  • chronic myelomonocytic leukemia
  • myelodysplastic syndromes
  • juvenile myelomonocytic leukemia
  • recurrent adult Burkitt lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood large cell lymphoma
  • recurrent follicular lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • refractory chronic lymphocytic leukemia
  • refractory multiple myeloma
  • chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • secondary myelodysplastic syndromes
  • multiple myeloma
  • adult lymphoblastic lymphoma
  • refractory anemia with excess blasts
  • refractory anemia
  • Burkitt lymphoma
  • childhood large cell lymphoma
  • adult Burkitt lymphoma
  • mantle cell lymphoma
  • childhood lymphoblastic lymphoma
  • childhood myelodysplastic syndromes
  • Primary Myelofibrosis
  • Anemia
  • Anemia, Refractory
  • Neoplasms
  • Hematologic Diseases
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Prolymphocytic
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia



Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455