Clinical trial NCT02395822: MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
Keywords: AML
Relapsed
Refractory
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2015-03-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: < 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
timeFrame: Day 42 post NK cell infusion
Secondary outcomes:
measure: In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
timeFrame: Day 14 post NK cell infusion
measure: Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
timeFrame: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42
measure: Treatment Related Mortality
timeFrame: 6 months post-therapy
measure: Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
timeFrame: Day 42 post NK cell infusion
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jeffrey Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.