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A Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (rhIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT02781467
Recruitment Status : Terminated (Business Decision)
First Posted : May 24, 2016
Last Update Posted : March 1, 2018
Information provided by (Responsible Party):
Celularity Incorporated

Brief Summary:

This study will find the highest acceptable treatment dose of cord blood, culture expanded natural killer (NK) cells, a kind of immune cell, in patients with relapsed and/or refractory acute myeloid leukemia.

The NK cells will be given with chemotherapy and Recombinant human interleukin 2 (rhIL-2) to help the NK cells expand in the body. The safety of this treatment will be studied and researchers want to learn if NK cells will help in treating the AML.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Biological: PNK-007 Drug: Cyclophosphamide Drug: Fludarabine Drug: Human recombinant Interleukin-2 (rhIL-2) Phase 1

Detailed Description:

The primary objective of the study is to assess safety and determine the maximum tolerated dose of PNK-007 in subjects with relapsed and/or refractory acute myeloid leukemia (AML). The secondary objective is to explore the potential clinical efficacy by day 42.

Treatment plan includes conditioning with cyclophosphamide and fludarabine. PNK-007 will administered IV followed by a total of six Recombinant human interleukin 2 (rhIL-2) injections to support the NK cells in the body.

Subjects will be followed for up to 24 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose Escalating Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (RHIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML).
Actual Study Start Date : July 11, 2016
Primary Completion Date : December 7, 2017
Study Completion Date : December 7, 2017

Arm Intervention/treatment
Experimental: Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2
Fludarabine Day -6 to -2 and Cyclophosphamide Day -5 and -4. On Day 0 PNK-007 at 4 varying dose levels followed by Human recombinant Interleukin-2 (rhIL-2) every other day, Day 0 to Day 10.
Biological: PNK-007 Drug: Cyclophosphamide Drug: Fludarabine Drug: Human recombinant Interleukin-2 (rhIL-2)

Primary Outcome Measures :
  1. Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 28 days ]
    Number and severity of adverse events within 28 days of administration.

  2. Maximum Tolerated Dose (MTD) [ Time Frame: Up to approximately 28 days ]
    The maximum dose safely administered for the treatment of patients with AML.

  3. Adverse Events (AEs) [ Time Frame: Up to approximately 12 months ]
    Number and severity of adverse events

Secondary Outcome Measures :
  1. Complete remission with incomplete platelet recovery (CRp) [ Time Frame: Up to approximately 42 days ]
    CRp is defined as leukemia clearance (< 5% marrow blasts and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery.

  2. Complete remission (CR) [ Time Frame: Up to approximately 42 days ]
    CR is defined as leukemia clearance (< 5% marrow blasts, no circulating peripheral blasts) in conjunction with normal values for absolute neutrophil count (> 1000/μL) and platelet count (> 100,000/μL), and independence from red cell transfusion.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject has an eligible disease:

    • Primary Acute myeloid leukemia (AML) induction failure: no Complete Remission (CR) after 2 or more induction attempts or
    • Relapsed AML: not in CR after 1 or more cycles of standard re-induction chemotherapy

      • For relapsed subjects > 60 years of age, the 1 cycle of standard re-induction chemotherapy is not required if either of the following criteria is met:
      • relapse within 6 months of last chemotherapy
      • blast count <30% within 10 days of starting this protocol therapy or
    • Secondary AML (MDS transformation or treatment related):


    • AML relapsed > 2 months after transplant Subjects 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 Visit 1.

  2. Subject is ≥ 18 and ≤ 70 years of age at the time of signing the informed consent form (ICF).
  3. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  4. Subject is willing and able to adhere to the study schedule and other protocol requirements.
  5. Karnofsky Performance Status > 50%.
  6. Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the PNK-007 cell infusion.
  7. Female of childbearing potential (FCBP) must:

    a. Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.

  8. Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting PNK-007, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy. Male subjects must: a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following PNK-007 discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Subject has any significant medical condition, laboratory abnormality, or known psychiatric illness that would prevent the subject from participating in the study.
  2. Subject has any condition including the presence of laboratory abnormalities which places the subject at unacceptable risk if he or she were to participate in the study.
  3. A subject has any condition that confounds the ability to interpret data from the study.
  4. Subject has a body weight exceeding 120kg.
  5. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) at screening.
  6. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening calculated using the Modification of Diet in Renal Disease Study equation or history of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below normal in the past year.
  7. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at screening.
  8. Subject has had prior treatment with biologic antineoplastic agents no less than 7 days before PNK-007 infusion and at least 5 half lives. For agents that have known Adverse Events (AEs) occurring beyond 7 days after administration (ie, monoclonal antibodies), this period must be extended beyond the time during which acute AEs are known to occur. An exception to this criteria is hydroxyurea which can be given throughout the Screening/Baseline Period up to the time of the pre-conditioning treatment.
  9. Subject has bi-phenotypic acute leukemia.
  10. Subject has had a transplant < 60 days prior to Visit 1 (Screening/Baseline visit).
  11. Subject has had treatment for graft-versus-host disease < 30 days prior to Visit 1 (Screening/Baseline visit).
  12. Subject is pregnant or breastfeeding.
  13. Subject has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or Computed tomography (CT) scan.
  14. Subject has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
  15. Subject is HIV positive.
  16. Subject has a history of malignancy except primary, secondary, or relapsed Acute myeloid leukemia (AML), or excised and cured non-melanoma skin cancer, or cervical carcinoma in situ that was surgically ablated more than 5 years prior to PNK-007 infusion.
  17. Subject has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease.
  18. Untreated chronic infection or treatment of any infection with systemic antibiotics within 2 weeks prior to dosing with PNK-007.
  19. Subject has any other organ dysfunction (CTCAE Version 4.03 Grade 3) that will interfere with the administration of the therapy according to this protocol.
  20. Subject has a resting left ventricular ejection fraction (LVEF) of < 35% obtained by echocardiography or multigated acquisition scan (MUGA).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02781467

United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Center
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Vanderbilt Univ Medical Center
Nashville, Tennessee, United States, 37232-6307
United States, Wisconsin
Froedtert Hospital BMT Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226-3522
Sponsors and Collaborators
Celularity Incorporated
Study Director: Monica E Luchi, MD Celularity Incorporated

Responsible Party: Celularity Incorporated
ClinicalTrials.gov Identifier: NCT02781467     History of Changes
Other Study ID Numbers: CCT-PNK-007-AML-001
First Posted: May 24, 2016    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: December 2017

Keywords provided by Celularity Incorporated:
Acute Myeloid
Human IL-2

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents