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Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells to Augment Single or Double Myeloablative Cord Blood Transplantation in Patients With Hematologic Malignancies


Phase 2
6 Months
45 Years
Open (Enrolling)
Both
Accelerated Phase Chronic Myelogenous Leukemia, 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, Childhood Myelodysplastic Syndromes, Chronic Eosinophilic Leukemia, Chronic Neutrophilic 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 Myelodysplastic Syndromes

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Trial Information

Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells to Augment Single or Double Myeloablative Cord Blood Transplantation in Patients With Hematologic Malignancies


PRIMARY OBJECTIVES:

I. Examine the safety and toxicity when ex vivo expanded cord blood cells are infused as an
off-the-shelf non-HLA matched product with the goal of providing rapid but transient
myelopoiesis in the setting of a single or double umbilical cord blood transplant.

II. Examine the in vivo persistence of the ex vivo expanded cord blood product. The kinetics
and durability of hematopoietic reconstitution will be determined and the relative
contribution to engraftment of the expanded cord blood product and the unmanipulated cord
blood unit(s) in early and long-term engraftment will be determined by frequent
determination of donor chimerisms in the peripheral blood.

SECONDARY OBJECTIVES I. Estimate the incidence and severity of acute and chronic
graft-versus-host-disease (GVHD) in patients receiving off-the-shelf ex vivo expanded and
cryopreserved cord blood cells.

II. Estimate the incidence of transplant related mortality at day 100. III. Estimate the
incidence of malignant relapse and probabilities of overall and event-free survival at 1 and
2 years post transplant.

IV. Obtain preliminary data on the incidence of infections/viral reactivation from the start
of conditioning to 100 days post transplant and then at 6 months, 1 year and 2 years post
transplant as possible.

V. Obtain preliminary data on the phenotype and function of immune cells recovering in
patients receiving expanded and unmanipulated cord blood grafts.

VI. Examination of possible immunologic factors leading to emergence of a dominant unit.

OUTLINE:

MYELOABLATIVE CONDITIONING: Patients receive fludarabine intravenously (IV) over 1 hour on
days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total-body
irradiation (TBI) twice daily on days -4 to -1.

TRANSPLANTATION: Patients undergo unmanipulated single- or double-unit umbilical cord blood
transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4
hours following the last unmanipulated cord blood infusion.

GVHD PROPHYLAXIS: Patients initially receive cyclosporine (CSP) IV over 1 hour beginning on
day -3. CSP may be given orally (PO) when the patient can tolerate oral medications and has
a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101
if there is no graft versus host disease. Patients also receive mycophenolate mofetil (MMF)
IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is
continued for a minimum of 30 days or until 7 days after blood counts recover whichever is
later. If there is no evidence of acute GVHD and donor CD3 engraftment is at least 50% from
one donor MMF may be tapered.


Inclusion Criteria:



- Acute myeloid leukemia:

- High risk complete response (CR)1 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 CR,
erythroblastic or megakaryocytic leukemia; >= 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 can not 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, Colleen Delaney 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

- 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 can not 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, Colleen Delaney 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 imatinib
mesylate

- Myelodysplasia International Prognostic Scoring System (IPSS) intermediate 2 (Int-2)
or High risk (i.e., refractory anemia with excess myeloblasts [RAEB], refractory
anemia with excess blasts in transformation [RAEB-T]) 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%

- Lansky (< 16 years old) >= 50%

- Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL
(adults)

- Calculated creatinine clearance must be > 60 mL/min (children < 18 years old)

- Total serum bilirubin must be < 3mg/dl and transaminases must be < 3 x the upper
limit of normal

- Diffusion capacity of carbon monoxide (DLCO) corrected > 50% normal; for pediatric
patients unable to perform pulmonary function tests, O2 saturation > 92% on room air

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

Outcome Measure:

Time to neutrophil and platelet engraftment

Outcome Description:

Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) >= 500.

Outcome Time Frame:

By day 30

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:

2378.00

NCT ID:

NCT01175785

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • 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
  • Childhood Myelodysplastic Syndromes
  • Chronic Eosinophilic Leukemia
  • Chronic Neutrophilic 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 Myelodysplastic Syndromes
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • 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, Neutrophilic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hypereosinophilic Syndrome
  • Anemia, Aplastic
  • Hematologic Neoplasms

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109