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Multi-center, Open-label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-the-shelf ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies


Phase 2
6 Months
45 Years
Open (Enrolling)
Both
Accelerated Phase Chronic Myelogenous Leukemia, Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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), Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia

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Trial Information

Multi-center, Open-label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-the-shelf ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies


PRIMARY OBJECTIVES:

I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in
patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented
with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not
receive the product.

SECONDARY OBJECTIVES:

I. Provide initial data on clinical and economic benefit, such as time to platelet
engraftment, duration of initial hospitalization, day 200 transplant related mortality (TRM)
and incidence of severe infections in the first 100 days post transplant.

II. The kinetics of immune system recovery will also be evaluated in both arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Standard of Care Arm:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30
minutes on days -8 to -6 and cyclophosphamide IV on days -7 to -6. Patients also undergo
total-body irradiation (TBI) twice daily (BID) on days -4 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood
(UCB) transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour
twice daily (adults) or three times a day (children) on days -3 to 100 with taper beginning
on day 101. Patients also receive mycophenolate mofetil (MMF) IV three times a day on days
0-7 then may receive MMF orally (PO) three times a day. Patients remain on MMF three times a
day for a minimum of 30 days, and then may begin taper if there is no evidence of
graft-versus-host disease (GVHD) and are well-engrafted from one donor unit.

Experimental Arm:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV and cyclophosphamide IV, and
undergo TBI as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day
0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4
hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV and mycophenolate mofetil IV or PO as in
Standard of Care Arm.

After completion of study treatment, patients are followed up periodically for 2 years.


Inclusion Criteria:



- Acute myeloid leukemia:

- High risk first complete remission (CR1) as evidenced by preceding
myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5
or 7, or as defined by referring institution treatment protocol), >= 2 cycles to
obtain complete remission (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% for age

- 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; these patients
must be discussed with the principal investigator prior to enrollment

- Acute Lymphoblastic Leukemia

- 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 or greater

- 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% for age

- 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; these patients
must be discussed with the principal investigator prior to enrollment

- Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in
first chronic phase (CP1) patient must have failed or be intolerant to tyrosine
kinase inhibitor therapy

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

- Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1

- Lansky (< 16 years old) >= 60

- Adults: calculated creatinine clearance must be > 60 mL and serum creatinine =< 2
mg/dL

- Children (< 18 years old): calculated creatinine clearance must be > 60 mL/min

- Total serum bilirubin must be < 3mg/dL unless the elevation is thought to be due to
Gilbert's disease or hemolysis

- Transaminases must be < 3 x the upper limit of normal

- Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal

- For pediatric patients unable to perform pulmonary function tests, oxygen (O2)
saturation > 92% on room air

- May not be on supplemental oxygen

- Left ventricular ejection fraction > 45%

- OR shortening fraction > 26%

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

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

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

- History of human immunodeficiency virus (HIV) infection

- Pregnant or breastfeeding

- If =< 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to engraftment (ANC greater than or equal to 500) in both arms (standard myeloablative CBT with and without off-the-shelf expanded cord blood progenitors)

Outcome Description:

The log-rank test will be used.

Outcome Time Frame:

Up to 2 years

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: Food and Drug Administration

Study ID:

2603.00

NCT ID:

NCT01690520

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • 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)
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Refractory Anemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • 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
  • Myelodysplastic Syndromes
  • Preleukemia
  • Anemia, Aplastic

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
University of ColoradoDenver, Colorado  80217
City of Hope Medical CenterDuarte, California  91010
Duke University Medical CenterDurham, North Carolina  27710
Dana-Farber Cancer Institute/Boston Children's HospitalBoston, Massachusetts  02115