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Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Primary Purpose

Leukemia, Acute Myeloid, Leukemia, Acute Lymphoblastic

Status
Completed
Phase
Phase 1
Locations
Belarus
Study Type
Interventional
Intervention
Expanded Haploidentical Natural Killer cells
IL-2
Sponsored by
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Acute Myeloid focused on measuring Immunotherapy, Natural killer cells

Eligibility Criteria

1 Year - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients:

  • Relapsed acute myeloid or lymphoblastic leukemia
  • Primary refractory myeloid or lymphoblastic leukemia
  • Karnofsky or Lansky performance scale greater or equal to 70
  • Written informed consent

Donor:

  • Haploidentical family donor
  • > 18 years old
  • Donor suitable for cell donation and apheresis according to standard criteria
  • Written informed consent

Exclusion Criteria:

Patients:

  • Uncontrolled infection
  • Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
  • Positive serology for human immunodeficiency virus (HIV)

Donors:

  • Pregnancy or breast feeding
  • Positive serology for HIV, hepatitis B or C.

Sites / Locations

  • Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NK cells + IL-2

Arm Description

After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events
Adverse events will be graded according to the CTCAE v4.0

Secondary Outcome Measures

Days of persistence of adoptively-transferred haploidentical NK cells
Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.
Occurrence of disease response
Analysis of blast cells content in bone marrow by cytomorphology or detection of MRD level by flow/PCR before and after immunotherapy.
Median time to leukocytes and platelets recovery
Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.
Number of T, B, NK, activated T and NK cells after immunotherapy
Analysis of T, B, NK, activated T and NK cells numbers (cells/microL) at +2, 6, 10, 14, 21, 28 days after NK infusion.

Full Information

First Posted
March 18, 2020
Last Updated
February 28, 2022
Sponsor
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
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1. Study Identification

Unique Protocol Identification Number
NCT04327037
Brief Title
Safety of Expanded Haploidentical Natural Killer Cells for Leukemia
Official Title
Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 2, 2019 (Actual)
Primary Completion Date
June 6, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.
Detailed Description
Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained. Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Myeloid, Leukemia, Acute Lymphoblastic
Keywords
Immunotherapy, Natural killer cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NK cells + IL-2
Arm Type
Experimental
Arm Description
After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1.
Intervention Type
Biological
Intervention Name(s)
Expanded Haploidentical Natural Killer cells
Intervention Description
One dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells
Intervention Type
Drug
Intervention Name(s)
IL-2
Other Intervention Name(s)
Ronkoleukinum
Intervention Description
6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Adverse events will be graded according to the CTCAE v4.0
Time Frame
1 months
Secondary Outcome Measure Information:
Title
Days of persistence of adoptively-transferred haploidentical NK cells
Description
Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.
Time Frame
1 months
Title
Occurrence of disease response
Description
Analysis of blast cells content in bone marrow by cytomorphology or detection of MRD level by flow/PCR before and after immunotherapy.
Time Frame
1 months post infusion
Title
Median time to leukocytes and platelets recovery
Description
Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.
Time Frame
2 months post infusion
Title
Number of T, B, NK, activated T and NK cells after immunotherapy
Description
Analysis of T, B, NK, activated T and NK cells numbers (cells/microL) at +2, 6, 10, 14, 21, 28 days after NK infusion.
Time Frame
1 months post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients: Relapsed acute myeloid or lymphoblastic leukemia Primary refractory myeloid or lymphoblastic leukemia Karnofsky or Lansky performance scale greater or equal to 70 Written informed consent Donor: Haploidentical family donor > 18 years old Donor suitable for cell donation and apheresis according to standard criteria Written informed consent Exclusion Criteria: Patients: Uncontrolled infection Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age Positive serology for human immunodeficiency virus (HIV) Donors: Pregnancy or breast feeding Positive serology for HIV, hepatitis B or C.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olga Aleinikova
Organizational Affiliation
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
City
Minsk
State/Province
Minsk Region
ZIP/Postal Code
223053
Country
Belarus

12. IPD Sharing Statement

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Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

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