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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


Phase 2
N/A
45 Years
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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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 MinnesotaMinneapolis, Minnesota  55455