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Haploidentical Donor Natural Killer (NK) Cell Infusion With Intravenous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Phase 1
18 Years
Open (Enrolling)
Acute Myelogenous Leukemia, Myelodysplastic Syndrome

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Trial Information

Haploidentical Donor Natural Killer (NK) Cell Infusion With Intravenous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Once the MTD/MED for IL-15 is determined, this cohort will be expanded to a total of 19
patients. The primary goal of this extended phase will be to establish a correlation of the
clinical endpoint, CRp defined as leukemic clearance (< 5% marrow blast and no peripheral
blood blasts) and neutrophil recovery without platelet recovery, with in vivo expansion.

Patients achieving a complete remission and neutrophil recovery (ANC > 500) for at least 4
weeks will be considered for allogeneic transplant to prolong remission independent of this

All patients, including those who go on to transplant, will be followed to determine disease
free survival, treatment related mortality, and time to relapse.

Inclusion Criteria:

- ≥ 18 years of age

- Meets one of the following disease criteria:

- Primary acute myelogenous leukemia (AML) induction failure: no complete response
(CR )after 2 or more induction attempts

- Relapsed AML or Secondary AML (from MDS or treatment-related): not in CR after 1
or more cycles of standard induction therapy. For patients > 60 years of age
the 1 cycle of standard chemotherapy is not required if either of the following
is met:

- relapse within 6 months of last chemotherapy

- blast count <30% within 10 days of starting protocol

- AML relapsed > 2 months after transplant who do not have the option of donor
lymphocyte infusions (e.g. recipients of autologous or umbilical cord blood
[UCB] transplants)

Patients with prior central nervous system (CNS) involvement are eligible provided that it
has been treated and cerebrospinal fluid (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 donor (3-5 of 6 HLA-A, B and C)

- Karnofsky Performance Status > 50%

- Adequate organ function defined as:

- Creatinine: ≤ 2.0 mg/dL

- Hepatic: Liver function tests (LFT's) < 5 times upper limit of institutional
normal (ULN)

- Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function
>50% corrected DLCO and FEV1 Testing required only if symptomatic or prior known

- Cardiac Function: Ejection fraction (EF) ≥ 40%, no uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities

- Able to be off prednisone or other immunosuppressive medications for at least 3 days
prior to Natural Killer (NK) cell infusion (excluding preparative regimen

- Women of child bearing potential and men with partners of child bearing potential
must agree to use effective contraception during therapy and for 4 months after
completion of therapy.

- Voluntary written consent

Exclusion Criteria:

- Bi-phenotypic acute leukemia

- Transplant < 60 days prior to study enrollment

- Pregnant or breastfeeding - The agents used in this study include those that fall
under Pregnancy Category D - have known teratogenic potential. Women of child bearing
potential must have a negative pregnancy test within 14 days of study treatment start

- Active autoimmune disease

- History of severe asthma, presently on chronic medications (a history of mild asthma
not requiring therapy is eligible)

- 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).
Surgical resection waives any waiting requirements.

- Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is

- Pleural effusion large enough to be detectable on chest x-ray

- Known hypersensitivity to any of the study agents used

- Received investigational drugs within the 14 days before enrollment

- Known active CNS involvement

Criteria For Initial Donor Selection:

- Related donors (sibling, parent, offspring, parent or offspring of an HLA identical

- 14-75 years of age

- At least 40 kilogram body weight

- In general good health as determined by the evaluating medical provider

- HLA-haploidentical donor/recipient match (low resolution)

- Not pregnant

- Agree to undergo donor viral screening panel

- Able and willing to undergo apheresis

- 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:

Maximum Tolerated/Minimum Efficacious Dose

Outcome Description:

Determine the maximum tolerated, minimum efficacious dose (MTD/MED) of recombinant human IL-15; dose limiting toxicity (DLT) occurring during the first 42 days after the NK cell infusion; MED = if 2 of 3 patients or 4 of 6 patients has an in vivo NK cell count >2500, then dose escalation with cease as it will be in the range of a biologic dose which may achieve the goal of in vivo expansion without pushing IL-15 doses higher to toxicity.

Outcome Time Frame:

Day 42

Safety Issue:


Principal Investigator

Jeffrey S Miller, MD

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:

October 2015

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • acute myelogenous leukemia
  • natural killer cells
  • haploidentical donor
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455