NCT02395822

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2015

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 16, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 24, 2015

Completed
6 months until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

January 10, 2018

Completed
Last Updated

February 20, 2018

Status Verified

December 1, 2017

Enrollment Period

1.2 years

First QC Date

February 16, 2015

Results QC Date

December 12, 2017

Last Update Submit

January 22, 2018

Conditions

Acute Myelogenous Leukemia

Keywords

AMLRelapsedRefractory

Outcome Measures

Primary Outcomes (1)

  • < 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L

    Without platelet recovery

    Day 42 post NK cell infusion

Secondary Outcomes (4)

  • In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)

    Day 14 post NK cell infusion

  • Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)

    Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42

  • Treatment Related Mortality

    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.

    Day 42 post NK cell infusion

Study Arms (1)

Preparative Regimen and SubQ rHuIL-15

EXPERIMENTAL

Preparative Regimen of Fludarabine and Cyclophosphamide IL-15 Activation of Donor NK Cells: IL-15 to Facilitate NK Cell Survival and Expansion

Biological: IL-15

Interventions

IL-15BIOLOGICAL

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

Also known as: Interleukin-15
Preparative Regimen and SubQ rHuIL-15

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Meets ONE of the following disease criteria:
  • Primary AML induction failure: no CR after 2 or more induction attempts
  • Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy
  • AML relapsed \> 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.
  • 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.

You may not qualify if:

  • 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).
  • years of age.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

  • Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, McKenna DH, Blazar BR, Weisdorf DJ, Miller JS. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019 Jul 9;3(13):1970-1980. doi: 10.1182/bloodadvances.2018028332.

    PMID: 31266741DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteRecurrence

Interventions

Interleukin-15

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

InterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Results Point of Contact

Title
Yumna Akhtar - Ct.gov Manager
Organization
University of Minnesota Masonic Cancer Center
akhta012@umn.edu
612-624-6313

Study Officials

  • Jeffrey Miller, MD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 16, 2015

First Posted

March 24, 2015

Study Start

October 1, 2015

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

February 20, 2018

Results First Posted

January 10, 2018

Record last verified: 2017-12

Locations

US(1)