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MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients

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ClinicalTrials.gov Identifier: NCT02395822
Recruitment Status : Completed
First Posted : March 24, 2015
Results First Posted : January 10, 2018
Last Update Posted : February 20, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE February 16, 2015
First Posted Date  ICMJE March 24, 2015
Results First Submitted Date December 12, 2017
Results First Posted Date January 10, 2018
Last Update Posted Date February 20, 2018
Actual Study Start Date  ICMJE October 1, 2015
Actual Primary Completion Date December 1, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2015)
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L [ Time Frame: Day 42 post NK cell infusion ]
Without platelet recovery
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02395822 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2018)
  • In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes) [ Time Frame: Day 14 post NK cell infusion ]
  • Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4) [ Time Frame: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42 ]
  • Treatment Related Mortality [ Time Frame: 6 months post-therapy ]
  • Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells. [ Time Frame: Day 42 post NK cell infusion ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2015)
  • In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes) [ Time Frame: Day 14 post NK cell infusion ]
  • IL-15 associated toxicity assessment [ Time Frame: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42 ]
  • Treatment Related Mortality [ Time Frame: 6 months post-therapy ]
  • Number of Subjects Achieving Complete Response With in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells. [ Time Frame: Day 42 post NK cell infusion ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Official Title  ICMJE MT2014-25: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
Brief Summary A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myelogenous Leukemia
Intervention  ICMJE Biological: IL-15

Preparative Regimen:

Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose)

IL-15 Activated Donor NK Cells:

The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.

IL-15 to Facilitate NK Cell Survival and Expansion:

IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total

Other Name: Interleukin-15
Study Arms Experimental: Preparative Regimen and SubQ rHuIL-15

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

Intervention: Biological: IL-15
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 Completed
Actual Enrollment  ICMJE
 (submitted: August 23, 2017)
17
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2015)
24
Actual Study Completion Date December 1, 2016
Actual Primary Completion Date December 1, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Recipient):

  • Meets ONE of the following disease criteria:

    1. Primary AML induction failure: no CR after 2 or more induction attempts
    2. Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy
    3. AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.
    4. Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:

      • Relapse within 6 months of last chemotherapy
      • BM blast count < 30% within 10 days of starting protocol therapy
  • Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A&B locus
  • Karnofsky Performance Status ≥ 60%
  • Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
  • Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
  • Agrees to use contraception prior to study entry and for the duration of study participation.

Exclusion Criteria (Recipient):

  • Bi-phenotypic acute leukemia.
  • Transplant < 60 days prior to study enrollment.
  • Active autoimmune disease.
  • History of severe asthma
  • Uncontrolled intercurrent illness
  • New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy
  • Pleural effusion large enough to be detectable on chest x-ray.
  • Pregnant women
  • History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection
  • Known hypersensitivity to any of the study agents used
  • Received investigational drugs within the 14 days of study registration.
  • Known active CNS involvement.

Criteria For Initial Donor Selection:

  • Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling).
  • 14-75 years of age.
  • At least 40 kilogram body weight.
  • In general good health as determined by the evaluating medical provider.
  • HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
  • Not pregnant.
  • Able and willing to undergo apheresis.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02395822
Other Study ID Numbers  ICMJE 2014LS092
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
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: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2017

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