Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Leukemia, Acute Lymphoblastic Clinical Trial

Official title:

Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04327037
• Other study ID #: BelarusianPediatric_NK_Pilot
• Status: Completed
• Phase: Phase 1
• Start date: January 2, 2019
• Est. completion date: June 30, 2021

Study information

• Verified date: February 2022
• Source: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 30, 2021
• Est. primary completion date: June 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Disease
• Leukemia
• Leukemia, Acute Lymphoblastic
• Leukemia, Acute Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Expanded Haploidentical Natural Killer cells
One dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells

Drug:
• IL-2
6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day.

Locations

Country	Name	City	State
Belarus	Belarussian Research Center for Pediatric Oncology, Hematology and Immunology	Minsk	Minsk Region

Sponsors (1)

Lead Sponsor	Collaborator
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Country where clinical trial is conducted

Belarus, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events	Adverse events will be graded according to the CTCAE v4.0	1 months
Secondary	Days of persistence of adoptively-transferred haploidentical NK cells	Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.	1 months
Secondary	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.	1 months post infusion
Secondary	Median time to leukocytes and platelets recovery	Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.	2 months post infusion
Secondary	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.	1 months post infusion