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Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML

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ClinicalTrials.gov Identifier: NCT03081780
Recruitment Status : Recruiting
First Posted : March 16, 2017
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE March 6, 2017
First Posted Date  ICMJE March 16, 2017
Last Update Posted Date March 15, 2019
Actual Study Start Date  ICMJE April 27, 2017
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2017)
Maximum tolerated dose (MTD) [ Time Frame: 3 months ]
Maximum FATE-NK100 dose which could be given to 3 participants such that not more than 1 participant experienced a DLT.
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2017)
Maximum tolerated dose (MTD) [ Time Frame: 3 months ]
Incidence of the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of FATE-NK100 administered intravenously (IV) in patients with refractory or relapsed acute myeloid leukemia (AML
Change History Complete list of historical versions of study NCT03081780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2017)
  • Clinical activity by CR/CRp leukemia clearance [ Time Frame: Day +42 ]
    Incidence of CRp defined as leukemia clearance (≤5%marrow blasts and no circulating peripheral blasts)
  • Clinical activity by CR/CRp neutrophil recovery [ Time Frame: Day +42 ]
    Incidence of CRp defined as neutrophil recovery (ANC >500 cells/microliter) but with incomplete platelet recovery
  • In vivo expansion of NK cells [ Time Frame: Day +14 ]
    Incidence of in vivo expansion (≥ 100 donor derived NK cells per uL blood) of NK cells
  • Treatment Related Mortality (TRM) [ Time Frame: 6 months ]
    Incidence of treatment related mortality (TRM)
  • Minimal residual disease (MRD) by bone marrow morphology [ Time Frame: up to Day 28 ]
    Incidence of minimal residual disease (MRD) clearance by bone marrow morphology after NK Cell infusion
  • Minimal residual disease (MRD) by flow cytometry [ Time Frame: up to Day 28 ]
    Incidence of minimal residual disease (MRD) clearance by flow cytometry after NK Cell infusion
  • Leukemia free survival (LFS) [ Time Frame: 1 year ]
    Incidence of Leukemia free survival (LFS)
  • Overall survival (OS) [ Time Frame: 1 year ]
    Incidence of overall survival (OS)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML
Official Title  ICMJE Open Label Dose Escalation Trial of an Adaptive Natural Killer (NK) Cell Infusion (FATE-NK100) With Subcutaneous IL-2 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
Brief Summary This is a Phase I open-label dose escalation study of a single infusion of FATE-NK100 and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy (CY/FLU) in subjects with refractory or relapsed acute myelogenous leukemia (AML). FATE-NK100 is a natural killer (NK) cell product that is enriched for NK cells with an "adaptive", or human cytomegalovirus (CMV)-induced, phenotype. The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a related donor (HLA-haploidentical or better but not fully HLA-matched) that is seropositive for cytomegalovirus (CMV+), and enriched for adaptive NK cells by depletion of CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells followed by ex-vivo culture expansion.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Refractory Acute Myelogenous Leukemia
  • Relapsed Acute Myelogenous Leukemia
Intervention  ICMJE Biological: FATE-NK100

Preparative regimen:

  • Fludarabine 25 mg/m2 x 5 days start Day -6
  • Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4

Apheresis cell collection (collected from the Donor Day - 8) will be enriched for FATE-NK100 per CMC. IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 6 doses with Dose 1 on Day 0 (no sooner than 4 hours post NK cells) and last dose no later than Day +12.

Study Arms Experimental: FATE NK-100
Intervention: Biological: FATE-NK100
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 29, 2017)
20
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2017)
29
Estimated Study Completion Date January 1, 2021
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- ≥18 but ≤ 70 years of age

  • Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:

    * Primary induction failure:

    ** De Novo AML: no CR after 2, 3 or 4 induction attempts with high dose chemotherapy

    • Secondary AML (from MDS or treatment related): no CR after 1, 2 or 3 cycles of high dose chemotherapy

      • Relapsed:
    • Not in CR after 1 or 2 cycles of standard re-induction therapy
    • Relapse diagnosed at the time of the 6 months post-HCT standard of care follow-up or later (i.e. based on bone marrow biopsy performed Day +170 or later) and without evidence of graft versus host disease (GVHD)

      • For patients > 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required.
  • Available HLA-matched or better but not fully HLA-matched (2/4 or 3/4 antigens) related donor (aged 18 to 75 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A and B locus who is CMV seropositive.
  • Karnofsky Performance Status ≥ 60%
  • Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:

    • Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 per current institutional calculation formula
    • Hepatic: AST and ALT ≤ 3 x upper limit of institutional normal
    • Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function >50% corrected DLCO and FEV1
    • Cardiac Function: LVEF ≥ 40% by echocardiography or MUGA
    • No symptomatic active conduction system abnormalities
  • Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to FATE-NK100 cell infusion (excluding preparative regimen premedications)
  • Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
  • Voluntary written consent prior to the performance of any research related procedures

Arm Specific Inclusion Criteria

High-Risk aGVHD (ARM 1):

- Pediatric or adult (ages 0-76 years) HCT recipients with high-risk acute GVHD, as determined either by the refined MN acute GVHD risk score [28]: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3) [31]. Patients in this arm must start treatment within the first 7 days after onset of high-risk aGVHD.

or

Steroid- Dependent aGVHD (ARM 2A):

- Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid-dependent acute GVHD, defined as any one of the following: Flare of acute GVHD of at least grade II/IV severity within 8 weeks of tapering down or (off of) immunosuppression for acute GVHD, with the flare occurring on ≤0.5 mg/kg prednisone. This can include late-onset aGVHD and overlap syndrome.

or

Steroid-Refractory aGVHD (ARM 2B):

- Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid refractory acute GVHD, defined as any one of the following:

  • No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
  • Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
  • Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
  • Flare of acute GVHD of at least grade II/IV severity while on steroids at a dose >0.5/mg/kg/day. This can include late-onset aGVHD and overlap syndrome.

Exclusion Criteria:

  • Myocardial Infraction (MI) within the previous 6 months
  • Acute leukemias of ambiguous lineage
  • Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test at screening
  • History of or known active CNS involvement with AML
  • Active autoimmune disease requiring systemic immunosuppressive therapy
  • History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
  • New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
  • Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
  • Received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03081780
Other Study ID Numbers  ICMJE 2016LS153
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Murali Janakiram, MD, MS University of Minnesota - Clinical and Translational Science Institute
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP