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A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors With an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies


Phase 1
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), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, 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, Prolymphocytic 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 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, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Chronic Lymphocytic Leukemia, Refractory Multiple Myeloma, 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 Lymphoblastic Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle 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 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 Lymphoblastic Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma

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Trial Information

A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors With an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies


PRIMARY OBJECTIVES:

I. Examine the safety and toxicity when ex vivo expanded cord blood cells are co-infused
with a second non-human leukocyte antigen (HLA)-identical cord blood graft following
myeloablative therapy in patients with hematologic malignancies.

II. Examine the in vivo persistence of the ex vivo expanded cord blood cells. The kinetics
and durability of hematopoietic reconstitution (time to engraftment defined as the first of
2 consecutive days in which the absolute neutrophil count [ANC] > 500) will be determined
and the relative contribution to engraftment of the expanded cord blood cells and the
unmanipulated cord blood cells in early and long-term engraftment will be determined by
donor chimerisms.

SECONDARY OBJECTIVES:

I. Estimate the incidence and severity of acute and chronic graft-versus-host disease (GVHD)
in patients receiving Notch-expanded 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 phenotype and function of immune cells recovering in
patients receiving expanded and unmanipulated cord blood grafts.

V. Obtain feasibility data on overnight shipment of ex vivo expanded progenitor cells for
infusion in patients are distant sites.

OUTLINE:

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

TRANSPLANTATION : On Day 0, patients undergo double-unit umbilical cord blood
transplantation which includes the infusion of one unmanipulated (not expanded) cord blood
unit followed 4 hours later by infusion of one ex vivo-expanded cord blood unit.

GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients initially receive cyclosporine IV beginning
on day -3. Cyclosporine may be given orally when the patient can tolerate oral medications
and has a normal gastrointestinal transit time. Cyclosporine is given until day 100, and may
taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV on
days -3 to 5 and then may receive oral MMF beginning day 6 to 30. MMF is stopped at Day 30
or 7 days after engraftment, whichever day is later, if no acute GVHD.

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


Inclusion Criteria:



- Patient has no existing 0-1 HLA-A, B, C, DRB1 and DQB1 matched related donor

- 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 HR 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%;

- 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 (< 5% blasts) and, recovery of
peripheral blood counts with no circulating blasts, may still be eligible;
reasonable attempts must be made to obtain an adequate specimen for morphologic
assessment, including possible repeat procedures

- 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);

- > 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 (< 5% blasts) and, recovery of
peripheral blood counts with no circulating blasts, may still be eligible;
reasonable attempts must be made to obtain an adequate specimen for morphologic
assessment, including possible repeat procedures

- Chronic Myelogenous Leukemia:

- Patients in blast crisis (BC) must receive therapy and must achieve accelerated
phase (AP)/chronic phase (CP) in order to be eligible (patients who remain in BC
are not eligible);

- If in first chronic phase, patient must have failed or be intolerant to imatinib
mesylate

- Myelodysplasia (MDS):

- International Prognostic Scoring System (IPSS) Int-2 or high risk (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% morphologically in representative bone marrow aspirate
(obtained < 2 weeks from enrollment)

- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma
(NHL) after initial therapy if stage III/IV in first partial remission (PR1) or after
progression if stage I/II < 1 year; Stage III/IV patients are eligible after
progression in complete response (CR)/partial response (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 Patient Care Conference [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 NHL > CR2/ > PR2:

- Patients in CR2/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

- Serum creatinine =< 2.0 mg/dL (adults) and creatinine clearance > 60 ml/min
(pediatrics)

- 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 > 3 mg/dL and symptomatic biliary disease will be excluded

- Diffusing capacity of the lung for carbon monoxide corrected (DLCOcorr) > 50% normal

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

- Karnofsky score >= 70% (adults) or Lansky score >= 50% (pediatrics)

Exclusion Criteria:

- Acute leukemia in relapse (>= 5% marrow blasts by morphology)

- Active central nervous system (CNS) leukemia involvement at the time of study
enrollment (cerebrospinal fluid with > 5 white blood cells (WBC)/mm^3 AND malignant
cells on cytospin)

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

- Female patients who are pregnant or breastfeeding

- Karnofsky performance status < 70% (adults) or Lanksy score < 50% (pediatrics)

- Prior autologous or allogeneic stem cell transplant with myeloablative preparative
regimen (If =< 18 years old, prior myeloablative transplant within the last 6 months)

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

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

- Seropositive for human immunodeficiency virus (HIV)

- Consenting 5 of 6 or 6 of 6 HLA-matched related donor available

- Unable to provide informed consent

- Use of any other experimental drug within 28 days of baseline

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Severe (grades 3 and 4) acute GVHD

Outcome Time Frame:

Up to day 100

Safety Issue:

Yes

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:

2044.00

NCT ID:

NCT00343798

Start Date:

April 2006

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)
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Burkitt Lymphoma
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Diffuse Large Cell Lymphoma
  • 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
  • Prolymphocytic 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 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
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Multiple Myeloma
  • 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 Lymphoblastic Lymphoma
  • Stage I Grade 3 Follicular Lymphoma
  • Stage I Mantle 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 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 Lymphoblastic Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Burkitt Lymphoma
  • 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
  • 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
  • Hematologic Neoplasms

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
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045