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IL-21-Expanded NK Cells for Induction of Acute Myeloid Leukemia (AML)

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: G-CSF (Drug); Fludarabine monophosphate (Drug); Cytarabine (Drug); Natural Killer (NK) Cell Infusion (Procedure)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Dean A. Lee, MD, PHD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Summary

The goal of this clinical research study is to learn about the safety and effects of giving special kinds of immune cells, called natural killer (NK) cells, with high dose chemotherapy to AML patients. Researchers want to learn the maximum tolerable number of NK cells that can be given. These NK cells may react against the leukemia cells, particularly when they are mismatched for certain HLA tissue type proteins. In addition to NK cells, you will receive cytarabine and fludarabine to try to kill any cancer cells and prevent rejection of the NK cells.

Clinical Details

Official title: 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

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

Primary outcome: Maximum Tolerated Dose (MTD) of mbIL21-Expanded Haploidentical NK Cells After Induction Chemotherapy with Fludarabine, Cytarabine, and G-CSF

Secondary outcome:

Complete Remission (CR) Assessment Following Infusion of the NK Cells

Donor NK-Cell Expansion

Detailed description: 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. Screening Tests: You had screening tests that are a routine part of the transplant preparation that helped show that you were eligible to take part in this study. 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 6 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.

About 4 hours later, you will receive cytarabine by vein over about 1 hour. If you are 60

years old or older, you will "rest" (not receive chemotherapy) on Day - 2.

On Day - 1, you will rest.

Three (3) times a week for 2 weeks, 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.

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 directions. 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 30 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility

Minimum age: 18 Years. Maximum age: 59 Years. Gender(s): Both.

Criteria:

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 immunosuppression. 2. Have a haploidentical family peripheral blood donor selected for best possible KIR reactivity. 3. Patient age >/= 18 years old. 4. Performance status: Karnofsky or Lansky Performance Scale (PS) greater or equal to 70. 5. Renal function: Serum creatinine /=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 /= 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 16 years of age or older and weigh at least 110 pounds. 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. Investigational therapies in the 4 weeks prior to beginning treatment on this protocol. 2. Congestive heart failure <6 months prior to screening. 3. Unstable angina pectoris <6 months prior to screening. 4. Myocardial infarction <6 months prior to screening. 5. 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, etc.).

Locations and Contacts

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: May 2014
Last updated: July 27, 2015

Page last updated: August 20, 2015

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