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Haploidentical Donor NK Cell Adoptive Therapy and Double T Cell Depleted Umbilical Cord Blood Transplantation With Post-Transplant IL-2 Immune Therapy For Refractory Acute Myeloid Leukemia


Phase 2
N/A
45 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Haploidentical Donor NK Cell Adoptive Therapy and Double T Cell Depleted Umbilical Cord Blood Transplantation With Post-Transplant IL-2 Immune Therapy For Refractory Acute Myeloid Leukemia


OBJECTIVES:

Primary

- To determine the rate of neutrophil engraftment and grade III-IV acute
graft-versus-host disease (GVHD) following a T cell depleted (TCD) umbilical cord blood
(UCB) transplantation without post-transplant immunosuppression followed by
administration of interleukin-2 (IL-2, aldesleukin) (every other day) days +3 to +13 to
expand NK cells in vivo.

Secondary

- To evaluate the safety of this regimen as assessed by monitoring the rates of graft
failure, acute GVHD, and transplant-related mortality (TRM).

- To perform quantitative, phenotypic, and functional assessments of the in vivo expanded
UCB-derived NK cells on (day +72).

- To assess clinical disease response (leukemia clearance and complete remission) and
survival duration in these patients.

- To evaluate the tolerability of aldesleukin in these patients.

- To evaluate the tolerance of IL-2

OUTLINE:

- Preparative regimen: Patients receive fludarabine phosphate intravenously (IV) over 1
hour on days -7 to -5 and cyclophosphamide IV on days -7 and -6. Patients undergo
total-body irradiation twice daily on days -5 to -2.

- Transplantation: Patients undergo T-cell depleted umbilical cord blood (UCB)
transplantation on day 0.

- IL-2 (Aldesleukin) therapy: Patients receive aldesleukin subcutaneously on days +3 6
doses every other day) and +60 (6 doses every other day).

Patients are followed periodically for up to 2 years after transplant.


Inclusion Criteria:



- Aged 0 to 45 years who meet one of the following criteria:

- Primary induction failure defined as no complete remission (CR) after two or
three induction cycles (no blast limit).

- Relapsed acute myeloid leukemia (AML) with low disease burden

- For patients 19 through 45 years of age: must have less than 10% marrow
blasts at time of enrollment for patients who did not receive re-induction
or measured at least 28 days from the start of re-induction therapy.
Patients who have relapsed more than 12 months following a prior
hematopoietic cell transplant (HCT) and did not reach CR following one
re-induction cycle but have less than 10% marrow blasts are eligible.

- For patients 0 through 18 years of age: must have less than 50% marrow
blasts after no more than 3 induction attempts

- CR3 or greater. This will include CRp defined as CR without platelet recovery to
100,000/mcL.

- CR1 or CR2 with high risk features (therapy induced, prior myelodysplastic
syndrome (MDS) or myeloproliferative disease (MPD), high risk cytogenetic or
molecular phenotype) with no available alternate (sibling, URD or UCB) donors.

- Patients with prior central nervous system (CNS) involvement are eligible provided
that it has been treated and is in remission. CNS therapy (chemotherapy or radiation)
should continue as medically indicated during the protocol.

- Have acceptable organ function within 14 days of enrollment defined as:

- Renal: creatinine ≤ 2.0 mg/dL (adult patients) or calculated creatinine
clearance > 40 ml/min (pediatric patients)

- Hepatic: bilirubin, AST/ALT, ALP ≤ 5 x upper limit of normal

- Pulmonary function: DLCOcorr > 50% of normal, (oxygen saturation [>92%] can be
used in child where PFT's cannot be obtained)

- Cardiac: left ventricular ejection fraction ≥ 45%

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

- Women of childbearing potential must agree to use adequate contraception (diaphragm,
birth control pills, injections, intrauterine device [IUD], surgical sterilization,
subcutaneous implants, or abstinence, etc.) for the duration of treatment.

- All patients will be questioned about prior exposure to antibody therapy (including
OKT3, rituximab, trastuzumab, and gemtuzumab) without affect to eligibility. Patients
with prior exposure will have a blood sample collected for human anti-mouse antibody
(HAMA). For patients with no prior antibody therapy exposure, no further action will
be taken.

- Not receiving prednisone or other immunosuppressive medications

- Voluntary written consent

Exclusion Criteria:

- Active infection at time of enrollment or documented fungal infection within 3 months

- Evidence of HIV infection or known HIV positive serology

- Pregnant or breast feeding. The agents used in this study may be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk. All
females of childbearing potential must have a blood test or urine study within 2
weeks prior to registration to rule out pregnancy.

- 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 of any alkylator chemotherapy
(etoposide >100 mg/m^2 x 5 days, cyclophosphamide >1 gm/m^2 or mitoxantrone >8
gm/m^2) delivered at 3-4 week intervals or > 6 months alkylator therapy (as above)
with extensive radiation (determined by Radiation Oncology, e.g. mantle irradiation
for Hodgkin's) and/or prior radiation therapy that makes a patient ineligible for
total body irradiation (TBI).

Criteria for Second Course of IL-2 (begin day +60):

- No Graft-Versus-Host Disease (GVHD), active infection or any other severe medical
co-morbidity

- Absolute neutrophil count (ANC) > 1000 without growth factor support

- No grade 4 toxicity (except fevers) attributed to IL-2 during course #1

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 Patients With Neutrophil Engraftment

Outcome Description:

Number of patient with absolute neutrophils >500*10^8/kg by 42 days post transplant.

Outcome Time Frame:

Day 42

Safety Issue:

No

Principal Investigator

Michael R. Verneris, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2008LS110

NCT ID:

NCT00871689

Start Date:

January 2009

Completion Date:

October 2011

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • 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)
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • childhood acute myeloid leukemia with 11q23 (MLL) abnormalities
  • childhood acute myeloid leukemia with inv(16)(p13;q22)
  • childhood acute myeloid leukemia with t(15;17)(q22;q12)
  • childhood acute myeloid leukemia with t(16;16)(p13;q22)
  • childhood acute myeloid leukemia with t(8;21)(q22;q22)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

University of Minnesota Children's Hospital - FairviewMinneapolis, Minnesota  55455