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

Acute Myelogenous Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395822
• Other study ID #: 2014LS092
• Status: Completed
• Phase: Phase 2
• First received: February 16, 2015
• Last updated: January 22, 2018
• Start date: October 1, 2015
• Est. completion date: December 1, 2016

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 1, 2016
• Est. primary completion date: December 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	< 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	In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)		Day 14 post NK cell infusion
Secondary	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
Secondary	Treatment Related Mortality		6 months post-therapy
Secondary	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