ZRx-101 (NK-92) for the Treatment of Refractory or Relapsed Acute Myeloid Leukemia

This study has suspended participant recruitment.
(Funding issues with the cell production)
Sponsor:
Collaborator:
Conkwest, Inc.
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00900809
First received: May 11, 2009
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

The ZRx-101 cells have features similar to activated NK cells, but mediate superior anti-tumor activity against hematologic and solid tumor targets in vitro and in vivo. The utilization of ZRx-101 cells as a form of adoptive immunotherapy offers several advantages relative to the use of activated NK cells.

The investigators propose to conduct an open label, dose escalation - deescalation Phase I clinical trial using ZRx-101 cells to determine the safety of the ZRx-101 cell line in patients with refractory or relapsed acute myeloid leukemia.

The investigators will also perform correlative studies using multi-parameter flow cytometry, the LUMINEX multianalytic profiling system and fluorescence in situ hybridization (FISH) to monitor the changes in the patient's immune system and changes in the receptor repertoire and cytotoxicity of the ZRx-101 cells after infusion.


Condition Intervention Phase
Acute Myeloid Leukemia
Biological: ZRx-101
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Adoptive Immunotherapy Using the Natural Killer Cell Line, ZRx-101 (NK-92), for the Treatment of Refractory or Relapsed Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To determine the safety / maximum tolerated dose of the ZRx-101 cell line in patients with refractory or relapsed acute myeloid leukemia [ Time Frame: 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the therapeutic efficacy of the ZRx-101 cell line in patients with refractory or relapsed acute myeloid leukemia [ Time Frame: 2011 ] [ Designated as safety issue: Yes ]
  • Determine the ZRx-101 cell receptor repertoire and cytotoxic activity using multi-parameter flow cytometry at different time intervals after the ZRx-101 cell infusion [ Time Frame: 2011 ] [ Designated as safety issue: No ]
  • Determine the presence of ZRx-101 cells, using fluorescence in situ hybridization (FISH), in the bone marrow [ Time Frame: 2011 ] [ Designated as safety issue: No ]
  • Determine the effects of ZRx-101 cells on the host immune system, using multi-parameter flow cytometry and the LUMINEX multianalytic profiling system, at different time intervals after the ZRx-101 infusion [ Time Frame: 2011 ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: September 2009
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: ZRx-101
    The ZRx-101 cells will be administered intravenously over 60 minutes. The starting dose of ZRx-101 cells will be 1 x 109 ZRx-101 cells/m2 (The 3 dose levels are: 1 x 109 cells/m2, 3 x 109 cells/m2 and 5 x 109 cells/m2). The second infusion will only be administered if no severe (grade >3) side effects due to the infusion of the ZRx-101 cells were encountered after the first infusion.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with acute myeloid leukemia that progressed or relapsed after two regimens of therapy. Patients must not have received radiotherapy, chemotherapy (with the exception of hydroxyurea which must be discontinued 72 hours prior to therapy) or biological therapy within the preceding 2 weeks and must have recovered from any adverse events due to prior administered agents
  • Assessable disease as measured by laboratory and bone marrow examinations
  • Age: Eighteen years or older
  • Performance status: ECOG ≤ 2 (Appendix A)
  • Serum creatinine ≤ 1.5 mg/ml and calculated creatinine clearance ≥ 50 mL/min (using the Cockcroft-Gault equation CL creatinine = ((140-age) x body mass X 0.85 if female)/72 x creatinine where age is given in years,body mass is given in Kg and creatinine is given in mg/dL)
  • Aspartate aminotransferase (AST) ≤ 59 IU/L
  • Alanine aminotransferase (ALT) ≤ 72 IU/L
  • Total bilirubin ≤ 1.3 mg/ml
  • Patients must have left ventricular ejection fraction (LVEF) ≥50 %
  • Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception
  • Ability to give informed consent
  • Life expectancy of greater than 3 months Note: as many of eligible patients will be pancytopenic secondary to their disease, hematologic abnormalities we will not be used as a criteria for entry or exclusion.

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia
  • Symptomatic central nervous system (CNS) involvement
  • History of congestive heart failure
  • Myocardial infarction in the past 6 months
  • Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
  • Concurrent treatment with corticosteroids and/or other immunosuppressive drugs
  • ECOG performance status >2 (Appendix A)
  • Hepatitis B or C or HIV positive serology
  • History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
  • Patient may not be receiving any other investigational agents
  • PT INR> 1.5 or patient is receiving systemic anticoagulation (e.g., warfarin)
  • Patient undergone autologous or allogeneic stem cell transplantation
  • History of another primary cancer except for curatively treated in situ cervical cancer and curatively resected non-melanoma skin cancer
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00900809

Locations
United States, Pennsylvania
UPMC Cancer Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Conkwest, Inc.
Investigators
Principal Investigator: Michael Boyiadzis, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Michael Boyiadzis, MD, University of Pittsburgh Medical Center
ClinicalTrials.gov Identifier: NCT00900809     History of Changes
Other Study ID Numbers: UPCI 06-118
Study First Received: May 11, 2009
Last Updated: February 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
Acute Myeloid Leukemia
ZRx101
Refractory
Refractory or Relapsed Acute Myeloid Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on April 22, 2014