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Cytokine-induced Memory-like NK Cells in Patients With AML or MDS

Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia, Myeloid, Acute

Intervention: Fludarabine (Drug); Cyclophosphamide (Drug); Leukapheresis (Procedure); Cytokine-induced killer cells (Biological); Aldesleukin (Biological)

Phase: Phase 1

Status: Recruiting

Sponsored by: Washington University School of Medicine

Official(s) and/or principal investigator(s):
Rizwan Romee, M.D., Principal Investigator, Affiliation: Washington University School of Medicine

Overall contact:
Rizwan Romee, M.D., Phone: 314-747-1385, Email: rromee@dom.wustl.edu


This phase I trial studies the side effects and best dose of activated natural killer cells in treating patients with relapsed or refractory acute myeloid leukemia and myeloid dysplastic syndromes. Giving chemotherapy before a donor natural killer cell infusion helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's natural killer cells. Modified natural killer cells may help the body build an immune response to kill cancer cells. Aldesleukin (interleukin-2) may stimulate the white blood cells (including natural killer cells) to kill leukemia cells.

Clinical Details

Official title: A Phase 1 Study of Cytokine-Induced Memory-Like NK Cells in Patients With AML or MDS

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximal tolerated dose (MTD) of CIML-NK cells

Secondary outcome:

Response assessed according to IWG criteria

Duration of remission (DOR)

Time to progression

Disease free survival (DFS)

Overall survival (OS)

Toxicity as measured by the frequency and incidence of serious adverse events


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Refractory AML without complete remission (CR) after induction therapy (primary induction

failure) or relapsed AML after obtaining a CR. OR High-risk AML (by ELN criteria; See Appendix C) in complete remission (CR) and has either refused hematopoietic stem cell transplantation OR is currently not eligible for hematopoietic stem cell transplantation OR for whom hematopoietic stem cell transplantation is being reserved for later relapse. This is inclusive of patients with minimal residual disease evidenced by cytogenetics, molecular testing, and/or flow cytometry. OR Myelodysplastic syndrome (MDS) with excess blasts (>5%) and progressive disease (see section 12. 4) at any time after initiation of DNA hypomethylator treatment during the past 2 years, OR failure to achieve complete or partial response or hematological improvement (see section 12. 4) after at least six cycles of azacytidine or four cycles of decitabine administered during the past 2 years, OR intolerance to azacytidine or decitabine. MDS patients with isolated 5q- abnormalities that meet these criteria after lenalidomide therapy and DNA hypomethylator therapy are also eligible.

- At least 18 years of age.

- Available HLA-haploidentical donor that meets the following criteria:

- Related donor (sibling, offspring, or offspring of sibling)

- At least 18 years of age

- HLA-haploidentical donor/recipient match by at least Class I serologic typing at

the A&B locus.

- In general good health, and medically able to tolerate leukapheresis required

for harvesting the NK cells for this study.

- Negative for hepatitis, HTLV, and HIV on donor viral screen

- Not pregnant

- Voluntary written consent to participate in this study

- Patients with known CNS involvement with AML are eligible provided that they have

been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.

- Karnofsky performance status ≥ 50 %

- Adequate organ function as defined below:

- Total bilirubin ≤ 2 mg/dl


- Creatinine within normal institutional limits OR creatinine clearance ≥ 50

mL/min/1. 73 m2 by Cockcroft-Gault Formula

- Oxygen saturation ≥90% on room air

- Ejection fraction ≥35%

- Able to be off of corticosteroids and any other immune suppressive medications

beginning on Day - 3 and continuing until 30 days after the infusion of the CIML NK


- Women of childbearing potential must have a negative pregnancy test within 28 days

prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period.

- Ability to understand and willingness to sign an IRB approved written informed

consent document (or that of legally authorized representative, if applicable). Exclusion Criteria:

- Relapsed after allogeneic transplantation.

- Circulating blast count ≥30,000/uL by morphology or flow cytometry (cytoreductive

therapies including leukapheresis or hydroxyurea are allowed).

- Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.

- Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive

of acute ischemia or active conduction system abnormalities.

- New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that

have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections).

- Known hypersensitivity to one or more of the study agents.

- Received any investigational drugs within the 14 days prior to the first dose of


- Pregnant and/or breastfeeding.

Locations and Contacts

Rizwan Romee, M.D., Phone: 314-747-1385, Email: rromee@dom.wustl.edu

Washington University School of Medicine, St. Louis, Missouri 63110, United States; Recruiting
Rizwan Romee, M.D., Phone: 314-747-1385, Email: rromee@dom.wustl.edu
Todd Fehniger, M.D., Ph.D., Sub-Investigator
Camille Abboud, M.D., Sub-Investigator
Amanda Cashen, M.D., Sub-Investigator
John DiPersio, M.D., Ph.D., Sub-Investigator
Meagan Jacoby, M.D., Ph.D., Sub-Investigator
Iskra Pusic, M.D., Sub-Investigator
Mark Schroeder, M.D., Sub-Investigator
Keith Stockerl-Goldstein, M.D., Sub-Investigator
Geoffrey Uy, M.D., Sub-Investigator
Ravi Vij, M.D., Sub-Investigator
Lukas Wartman, M.D., Sub-Investigator
John Welch, M.D.,Ph.D., Sub-Investigator
Peter Westervelt, M.D., Ph.D., Sub-Investigator
Additional Information

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Related publications:

Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1915-9. doi: 10.1073/pnas.0813192106. Epub 2009 Jan 30.

Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, Cooper MA, Fehniger TA. Cytokine activation induces human memory-like NK cells. Blood. 2012 Dec 6;120(24):4751-60. doi: 10.1182/blood-2012-04-419283. Epub 2012 Sep 14.

Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012 Dec 17;209(13):2351-65. doi: 10.1084/jem.20120944. Epub 2012 Dec 3.

Starting date: August 2014
Last updated: June 1, 2015

Page last updated: August 23, 2015

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