NCT01639456

CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploid Donor Natural Killer Cell Treatment in Older AML in First Complete Remission

A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy in Older Adults With Acute Myelogenous Leukemia in First Complete Remission

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II trial designed to test the safety and efficacy (disease free survival \[DFS\]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML). The natural killer (NK) cell product will be given to patients 60 years and older who are in a first complete remission after 1 or 2 courses of standard AML induction. After a preparative regimen of cyclophosphamide and fludarabine, patients will receive a single infusion of either CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.

Detailed description

The trial will use a single-stage design and will take place in two parts. The first part will support the selection of the better NK cell product as measured by in vivo NK cell expansion. Successful in vivo NK cell expansion is defined as 40% donor DNA and 40% of lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post infusion. Part 1: 1:1 randomization with 10 patients per cohort to either: 1. CD3-/CD19- NK cell product or 2. CD3-/CD56+ purified NK cell product The product with better NK cell expansion will be used for the rest of the trial. If the results and safety profile are equivalent, the CD56+ selection approach will be used. If neither approach results in successful NK cell expansion, the trial will be stopped and the platform redesigned. Part 2: complete the trial by enrolling an additional 26 patients using the product deemed successful during part 1 to estimate the primary endpoint (DFS at 12 months)

Conditions

• Acute Myelogenous Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	CD3-/CD19- natural killer cells	Infused on Day 0. The final CD3-/CD19- product must contain at least 20% NK cells based on previous studies using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
BIOLOGICAL	CD3-CD56+ natural killer cells	Infused on Day 0. The final CD3-/CD56+ product must contain at least 70% NK cells based on a previous study using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
DEVICE	CliniMACS® CD3 and CD19 Reagent System	In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
DEVICE	CliniMACS® CD56 Reagent System	CliniMACS® CD3 and CD19 Reagent System will be used in addition to CliniMACS® CD56 Reagent System to enrich CD56+ NK cells. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
DRUG	Cyclophosphamide	Infused intravenously 60 mg/kg x day -5
DRUG	Fludarabine	Fludarabine 25 mg/m2 x days -6 through -2
DRUG	Aldesleukin	IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.

Timeline

• Start date: 2013-10-01
• Primary completion: 2017-01-01
• Completion: 2017-01-01
• First posted: 2012-07-12
• Last updated: 2017-12-02

Locations

2 sites across 1 country: United States