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)

NCT02781467 | Terminated Phase 1 DMC

• 1 other identifier: CCT-PNK-007-AML-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 7

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.

Conditions

Leukemia, Myeloid, Acute

Keywords

Acute Myeloid; Leukemia; PNK-007; Human IL-2; RHIL-2; Fludarabine; Cyclophosphamide

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  Number and severity of adverse events within 28 days of administration.

  Up to approximately 28 days

• Maximum Tolerated Dose (MTD)

  The maximum dose safely administered for the treatment of patients with AML.

  Up to approximately 28 days

• Adverse Events (AEs)

  Number and severity of adverse events

  Up to approximately 12 months

Secondary Outcomes (2)

• Complete remission with incomplete platelet recovery (CRp)

  Up to approximately 42 days

• Complete remission (CR)

  Up to approximately 42 days

Study Arms (1)

Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2

EXPERIMENTAL

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)

Interventions

PNK-007 BIOLOGICAL

Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2

Cyclophosphamide DRUG

Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2

Fludarabine DRUG

Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2

Human recombinant Interleukin-2 (rhIL-2) DRUG

Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has any significant medical condition, laboratory abnormality, or known psychiatric illness that would prevent the subject from participating in the study.
• 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.
• A subject has any condition that confounds the ability to interpret data from the study.
• Subject has a body weight exceeding 120kg.
• Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) at screening.
• 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.
• Subject has a bilirubin level \> 2 mg/dL (unless subject has known Gilbert's disease) at screening.
• 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.
• Subject has bi-phenotypic acute leukemia.
• Subject has had a transplant \< 60 days prior to Visit 1 (Screening/Baseline visit).
• Subject has had treatment for graft-versus-host disease \< 30 days prior to Visit 1 (Screening/Baseline visit).
• Subject is pregnant or breastfeeding.
• Subject has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or Computed tomography (CT) scan.
• Subject has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.

Sponsors & Collaborators

• Celularity Incorporated: lead

Study Sites (7)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt Univ Medical Center

Nashville, Tennessee, 37232-6307, United States

Location

Froedtert Hospital BMT Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Solveig Ericson, MD

  Celularity Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: May 24, 2016
• Study Start: July 11, 2016
• Primary Completion: December 7, 2017
• Study Completion: December 7, 2017
• Last Updated: July 22, 2020

Record last verified: 2017-12

Locations

US (7)