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Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases

Phase 2
18 Years
75 Years
Open (Enrolling)
Acute Myeloid Leukemia, Myelodysplastic Syndrome

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Trial Information

Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases

A reduced intensity conditioning will start on day -18, followed by infusion of adult donor
NK (natural killer) cells on day-12, 6 doses of interleukin-2 (IL-2) to promote NK expansion
(day -12 to day -2), and infusion of a CD34+ selected haploidentical graft followed by ATG
on day 0, +1 and +2.

Inclusion Criteria:

- Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

RAEB-1 or RAEB-2 fitting within one of the following disease groups:

- Primary induction failure (PIF): Patients who have not achieved a complete remission
(CR) after two induction cycles of cytotoxic therapy (i.e. 7+ 3, MEC, FLAG, etc.) and
having <30% blasts by morphology and < 2500 absolute circulating blasts. (Measured at
least 21 days from prior therapy.) Demethylating agents do not count as induction
therapy; however early re-induction therapy based on residual disease on a day 14 BM
will count as a 2nd cycle

- Relapsed Disease with low disease burden (AML or MDS with <30% blasts by morphology
and < 2500 absolute circulating blasts):

No re-induction attempts are required, but a maximum of 2 reinduction attempts are allowed
to be eligible.

- CR3 or greater: This will include CRp defined as CR without platelet recovery to

- CR1 or CR2 with high risk features: Includes therapy induced, prior MDS or MPD, high
risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated

Patients with known prior central nervous system (CNS) involvement are eligible provided
that it has been treated and CSF is clear for at least 2 weeks prior to enrollment. CNS
therapy (chemotherapy or radiation) should continue as medically indicated during the
study treatment.

- Available related HLA-haploidentical adult donor by at least Class I serologic typing
at the A&B locus

- Karnofsky score > 50%

- Adequate organ function within 28 days of study registration defined as:

- Hepatic: AST ≤ 3 x upper limit of institutional normal, total bilirubin ≤ 2.0

- Renal: estimated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m^2

- Pulmonary: Oxygen saturation ≥ 90% on room air and DLCOcor ≥ 40%

- Cardiac: Ejection Fraction ≥ 35% and no uncontrolled angina, severe uncontrolled
ventricular or arterial arrhythmias, or any evidence of acute ischemia or active
conduction system abnormalities (rate controlled atrial fibrillation is not an

- Able to be off prednisone or other immunosuppressive medications for at least 3 days
prior to NK cell infusion (except for those prescribed as part of the study)

- Women of child bearing potential must have a negative pregnancy test within 14 days
prior to study registration and agree to use adequate birth control during study

- Voluntary written consent

Exclusion Criteria:

- Biphenotypic leukemia

- Prior allogeneic transplant for AML within previous 6 months

- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to
infection must be stable/improving (with associated clinical improvement) after 1
week of appropriate therapy (4 weeks for presumed or documented fungal infections).

- Uncontrolled bacterial, fungal or viral infections including HIV - chronic
asymptomatic viral hepatitis is allowed

- Known hypersensitivity to any of the study agents

- Received any investigational drugs within the 14 days before 1st dose of fludarabine

- Requires hydrea or other agents to control blast count

Donor Selection:

- Related donor (sibling, parent, offspring, parent or offspring of an HLA identical
sibling) 12-75 years of age. (It is recognized individual institutions may have
differing donor age guidelines. This is acceptable as long as no donor is younger
than 12 years or older than 75 years).

- At least 40 kilograms

- In general good health as determined by the medical provider

- HLA-haploidentical donor/recipient match by at least Class I serologic typing at the
A&B locus

- Able and willing to have up to 4 separate apheresis collections

- Not pregnant

- Voluntary written consent

Type of Study:


Study Design:

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

Outcome Measure:

Rate of Donor Neutrophil Engraftment

Outcome Description:

The rate of donor neutrophil engraftment in the absence of leukemia at day +28 will be determined. Successful neutrophil engraftment is defined as an absolute donor-derived neutrophil count of >500 cells/μl. Leukemia free is defined as <5% bone marrow blasts, absence of blasts with Auer rods; absence of extramedullary disease; but cytogenetic or molecular minimal residual disease is allowed.

Outcome Time Frame:

Day 28

Safety Issue:


Principal Investigator

Sarah Cooley, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

September 2015

Related Keywords:

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • non-myeloablative haploidentical transplant
  • hematopoietic cell transplant
  • natural killer cells
  • adoptive cellular therapy
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Emory University Atlanta, Georgia  30322
Ohio State University Columbus, Ohio  43210
Washington University St. Louis, Missouri  63110
University of Minnesota, Masonic Cancer Center Minneapolis, Minnesota  55455