Transplantation of Umbilical Cord Blood for Myeloid Leukemia Patients Not in CR With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen and UCB NK Cells
N/A
45 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
Transplantation of Umbilical Cord Blood for Myeloid Leukemia Patients Not in CR With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen and UCB NK Cells
OBJECTIVES:
Primary
- Determine the incidence of 6-month disease free survival. The primary laboratory
objective is the measure of in vivo expansion of umbilical cord blood (UCB) derived
natural killer cells (NK) after a fully ablative preparative regimen.
Secondary
- Determine the incidence of transplant-related mortality at 6 months after NK UCB +
double UCBT
- Evaluate the pattern of chimerism after NK UCB + double UCBT
- Determine the incidence of neutrophil engraftment at day 42 after NK UCB + double
umbilical cord blood transplantation (UCBT)
- Determine the incidence of platelet engraftment at 6 months after NK UCB + double UCBT
- Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade
III-IV at day 100 after NK UCB + double UCBT
- Determine the incidence of chronic GVHD at 1 year after NK UCB + double UCBT
- Determine the disease-free survival at 1 after NK UCB + double UCBT
- Determine the incidence of relapse at 1 after NK UCB + double UCBT
OUTLINE: This is a single arm, nonrandomized, open-label study.
- Myeloablative conditioning regimen: Patients receive fludarabine intravenously (IV)
over 1 hour on days -18 to -16 and cyclophosphamide intravenously (IV) on days -18 and
-17. Patients undergo total-body irradiation twice daily on days -16 to -13.
- Haploidentical umbilical cord blood (UCB) natural killer (NK) cell therapy and
aldesleukin: Patients undergo haploidentical UCB-enriched NK cell (CD3- depleted)
infusion on day -13. Patients then receive aldesleukin subcutaneously on days -13, -11,
-9, -7, -5, and -3. Some patients may also receive methylprednisolone IV on days -1 and
0.
- UCB transplantation (UCBT): Patients undergo a single or double UCBT on day 0.
Beginning on day 1, patients receive filgrastim (G-CSF) IV once daily until blood
counts recover.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours
2-3 times daily beginning on day -1 and continuing until day 100, followed by a taper
until day 180. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily
beginning on day -1 and continuing until day 30 (or 7 days after engraftment) in the
absence of acute GVHD.
Inclusion Criteria:
- Diagnosis of 1 of the following:
- Acute myeloid leukemia with active leukemia (i.e., not in complete remission
[CR]), defined by light microscopy (bone marrow) and having failed ≥ 1 round of
standard chemotherapy
- Chronic myelogenous leukemia with myeloid blast crisis not in second chronic
phase after ≥ 1 course of standard chemotherapy and imatinib mesylate
- Myelodysplastic syndromes (MDS) or other myeloproliferative disorders more than
10% blasts after ≥ 1 course of standard chemotherapy
- Unrelated umbilical cord blood (UCB) donor(s) available - Each unit must be 4-6/6
HLA-A, -B, and -DRB1 matched with the recipient (and to each other if 2 units are
utilized) (for UCB graft) AND 3/6 HLA-A, -B, and -DRB1 matched with the recipient
(for UCB natural killer [NK] cells)
- Karnofsky performance status (PS) 80-100% (adult patients) or Lansky PS 50-100%
(pediatric patients)
- Creatinine ≤ 2.0 mg/dL (adult patients) OR creatinine clearance > 40 mL/min
(pediatric patients)
- Bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline
phosphatase ≤ 5 times upper limit of normal (ULN)
- Corrected Carbon Monoxide Diffusing Capacity (DLCO) > 50% normal OR oxygen saturation
> 92% (in pediatric patients who cannot undergo pulmonary function tests)
- Left ventricular ejection fraction ≥ 45%
Exclusion Criteria:
- Pregnant or nursing
- Positive pregnancy test (Fertile patients must use effective contraception)
- History of HIV infection
- Active infection at time of transplantation
- Active infection with Aspergillus or other mold within the past 120 days
- Less than 6 months since prior myeloablative transplant (≤ 18 years old)
- Prior myeloablative allotransplant or autologous transplant (> 18 years old)
- No prior extensive therapy including > 12 months of any alkylator chemotherapy or > 6
months of alkylator therapy with extensive radiation (e.g., mantle irradiation for
Hodgkin's lymphoma)
- Prior radiation therapy that would make the patient ineligible for total-body
irradiation
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants (Patients) Who Were Disease-free and Alive at 6 Months
Outcome Description:
Number of patients who were alive and free of disease (malignancy) at 6 months after transplant.
Outcome Time Frame:
6 Months Post Transplant
Safety Issue:
No
Principal Investigator
Jeffrey Miller, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
UMN-2005LS058
NCT ID:
NCT00354172
Start Date:
February 2006
Completion Date:
August 2008
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- 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)
- atypical chronic myeloid leukemia
- blastic phase chronic myelogenous leukemia
- childhood chronic myelogenous leukemia
- previously treated myelodysplastic syndromes
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- relapsing chronic myelogenous leukemia
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- childhood myelodysplastic syndromes
- Leukemia
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
