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A Phase I/II Clinical Trial Testing the Safety and Feasibility of IL-21-Expanded Natural Killer Cells for the Induction of Relapsed/Refractory Acute Myeloid Leukemia

Phase 1/Phase 2
18 Years
59 Years
Not Enrolling

Thank you

Trial Information

A Phase I/II Clinical Trial Testing the Safety and Feasibility of IL-21-Expanded Natural Killer Cells for the Induction of Relapsed/Refractory Acute Myeloid Leukemia

While growing the NK cells from the blood in the lab, mismatched T cells may also grow,
which can cause a reaction against normal tissue called graft-vs-host disease (GvHD). In
the lab, the T cells will be removed from the cell product using special magnets and
antibody-coated magnetic beads. The drug aldesleukin (interleukin-2) is then added to the
NK cells to improve their function. The aldesleukin will be washed out of the cell product
before it is given to you.

The NK cells will be donated from a family member who has a certain genetic type in their
blood called HLA that partly matches yours.

If you agree to take part in this study, you will be assigned to a dose level of NK cells
based on when you joined this study. The first group of participants will receive the
lowest dose level. Each new group will receive a higher dose than the group before it, if
no intolerable side effects were seen. This will continue for up to 8 dose levels or until
the highest tolerable dose of NK cells is found. One (1) to 10 participants will be treated
in each dose level.

The day you receive the first NK cell infusion is called Day 0. The days before you receive
your NK cell infusion are called minus days (D-). The days after you receive the NK cell
infusion are called plus days (D+).

Study Drug Administration:

On Days -6, -5, -4, -3, and -2, you will receive fludarabine by vein over about 30 minutes.
You will then receive cytarabine by vein over about 1 hour.

On Day -1, you will "rest" (not receive chemotherapy).

On Days 0, +2, +4, +7, +9, and +11, you will receive NK cells by vein over 30 minutes. You
will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

You will receive filgrastim as an injection under the skin 1 time a day, starting on Day -7
and continuing until your white blood cell levels are high enough. Filgrastim is designed
to help with the growth of white blood cells.

Study Visits:

Before treatment starts:

- Your medical history will be recorded.

- You will have a physical exam, including measurement of your vital signs (blood
pressure, heart rate, temperature, and breathing rate).

- Blood (about 2 teaspoons) will be drawn for routine tests.

On Days 0, +2, +4, +7, +9, and +11, before each NK cell infusion:

- Your medical history will be recorded.

- You will have a physical exam, including measurement of your vital signs.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- The amount of oxygen in your blood will be measured by placing a sensor on the tip of
your finger.

Twice a week, while your blood counts are low, you will have blood (about 2 teaspoons)
drawn for routine tests.

Once your blood counts are high enough, you will have blood (about 2 teaspoons) drawn for
routine tests once a week until Day +56.

Once your blood counts are high enough or around Day +28 (whichever is earlier), you will
have a bone marrow aspiration and biopsy to check the status of the disease and DNA tests to
check if the cells in your bone marrow are yours or your NK cell donor's. To collect a bone
marrow aspiration/biopsy, an area of the hip or other site is numbed with anesthetic, and a
small amount of bone marrow and bone is withdrawn through a large needle.

Blood (about 2 teaspoons) will be drawn to test the genetic makeup and function of the
infused NK cells and to check the status of the disease:

- Before treatment starts.

- Before and about 1-3 hours after each NK cell infusion.

- Once a day on Days +14, +16, +18, +21, and then weekly until Day +56.

Length of Study:

Your participation on the study will be over on Day +56.

You will be taken off study early if the disease gets worse, if intolerable side effects
occur, if not enough NK cells can be collected, or if you are unable to follow study

This is an investigational study. Cytarabine, fludarabine, and filgrastim are FDA approved
and commercially available for the treatment of AML. The investigational part of this study
is to find the best dose of NK cells that can be given with the goal of helping to prevent
the cancer from coming back. The way the researchers process the NK cells is
investigational and is not FDA approved.

Up to 58 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with relapsed or primary refractory AML. Patients with relapsed AML after
allogeneic stem cell transplantation, including those who have received donor
lymphocyte infusions, are eligible if they have no active GvHD and are off

2. Have a haploidentical family peripheral blood donor selected for best possible KIR

3. Patient age between 18 and 59 years, inclusive.

4. Performance status: Zubrod 70%.

5. Renal function: Serum creatinine than 40 cc/min. Creatinine for pediatric patients limit of normal for age (whichever is less).

6. Pulmonary function: FEV1, FVC and DLCO >/=50% of expected, corrected for hemoglobin.
For pediatric patients, if unable to perform pulmonary function tests (most children
< 7 years of age), pulse oximetry >/= 92% on room air by pulse oximetry.

7. Liver function: Total bilirubin Gilbert's syndrome) and SGPT (ALT)
8. Cardiac function: left ventricular ejection fraction >/= 40%. No uncontrolled
arrhythmias or uncontrolled symptomatic cardiac disease.

9. Negative serum test to rule out pregnancy within 2 weeks prior to registration in
females of childbearing potential (non childbearing potential defined as
premenarchal, greater than one year post-menopausal, or surgically sterilized).

10. Sexually active males and females of childbearing potential must agree to use a form
of contraception considered effective and medically acceptable by the Investigator.

11. Negative serology for human immunodeficiency virus (HIV).

12. Donor Eligibility Criteria and Evaluation Prior to Donation: Donor must be 18 years
of age or older.

13. Donor must be an HLA-haploidentical relative selected for best NK alloreactivity,
defined as having a KIR gene present on the Donor NK cells for which the relevant HLA
haplotype (KIR ligand) is absent in the Recipient and present in the Donor.

14. Donor must meet standard institutional eligibility and donor certification criteria
for therapeutic cell product donation.

15. Not be pregnant as defined by negative serum (beta HCG) pregnancy test in females of
childbearing potential (Non-childbearing potential defined as premenarchal, previous
surgical sterilization, or postmenopausal for >12 months.

16. Evaluation: History and physical examination. Laboratory examinations: hematology,
electrolytes, chemistry. Infectious disease screening and serology. HLA typing.

Exclusion Criteria:

1. Failed to attain remission with any previous FLAG therapy.

2. Investigational therapies in the 4 weeks prior to beginning treatment on this

3. Congestive heart failure <6 months prior to screening.

4. Unstable angina pectoris <6 months prior to screening.

5. Myocardial infarction <6 months prior to screening.

6. Uncontrolled infection, defined as an infection which has not resolved spontaneously
or does not show evidence of significant resolution after initiating appropriate
therapy, excluding chronic asymptomatic viral infections (e.g., HPV, BK virus, HCV,

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 Dose (MTD)

Outcome Description:

Maximum tolerated dose defined as highest dose studied in which 6 patients have been treated and at most 2 patients with dose-limiting toxicities (DLTs) observed. A dose-limiting toxicity (DLT) is defined as: Acute severe (grade 3 or 4) infusional allergic reaction related to the NK cells infusion. Prolonged cytopenia beyond D+28. If neutropenia is still present at day 28, that will trigger the designation of prolonged neutropenia as a DLT. If neutrophil counts have recovered by day 28, then no DLT will have occurred. In either case, the status of neutrophil recovery beyond day 28 will not change the designation of DLT or No DLT made at day 28. Acute GvHD overall grade 3 or 4. Severe (grade 3 or 4) unexpected toxicity related to the NK cell infusion.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Dean A. Lee, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2013

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Acute Myeloid Leukemia
  • Blood And Marrow Transplantation
  • Natural killer cells
  • NK
  • mbIL21-expanded haploidentical NK cells
  • G-CSF
  • Filgrastim
  • Neupogen
  • Fludarabine monophosphate
  • Fludarabine Phosphate
  • Fludara
  • Cytarabine
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



UT MD Anderson Cancer Center Houston, Texas  77030