Safety and Efficacy Study of Donor Natural Killer Cells Given After Haploidentical Hematopoietic Cell Transplantation

Acute Lymphoblastic Leukemia Clinical Trial

— DNKI-II  

Official title:

HLA-Haploidentical Hematopoietic Cell Transplantation and Subsequent Donor Natural Killer Cell Infusion in Refractory Acute Leukemia - A Phase 1-2a STUDY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01795378
• Other study ID #: AMC 2012-0478
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 18, 2013
• Last updated: December 29, 2015
• Start date: February 2013
• Est. completion date: May 2015

Study information

• Verified date: December 2015
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The protocol treatment is to evaluate clinical effects of donor-derived natural killer cells that are given after HLA-mismatched hematopoietic cell transplantation.

Description:

Those patients with acute leukemia, which is not responding to coventional chemotherapy, will be treated. The clinical effects will be evaulated in terms of safety (side effects) and anti-leukemia effect.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years and older

Eligibility

Inclusion Criteria:

Patients with acute leukemia, which are refractory to standard treatment. Patients should be 17 years of age or older. The performance status of the patients should be 70 or over by Karnofsky scale. Patients should not have excessive hepatic dysfunction (bilirubin less than 3.0 mg/dl, AST less than 5 times the upper normal limit).

Patients should not have excessive renal dysfunction (creatinine less than 3.0 mg/dl).

Patients should not have clinically-evident cardiac or pulmonary dysfunction. Patients and donors must sign informed consent.

Exclusion Criteria:

Patients who are pregnant or lactating are not eligible.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• donor natural killer cell infusion
Donor NK cells will be generated at the GCP laboratory at Asan Institute of Life Science by a team from Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology. The patients will receive donor NK cell infusion (DNKI) around on days 6 and 9 (generated from the first collection), and around on days 13 and 20 (generated from the second collection). For DNKI to be given on days 6 and 9, a 3-patient cohort each will receive escalating dose of 2x10e7/kg, 5x10e7/kg, 1x10e8/kg, and 1-4 x10e8 cells. The dose of DNKI to be given on days 13 and 20 will be 1-4 x10e8/kg.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Korea Research Institute of Bioscience and Biotechnology

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011 Sep 1;118(9):2609-17. doi: 10.1182/blood-2011-02-339838. Epub 2011 Jun 28. — View Citation

Yoon SR, Lee YS, Yang SH, Ahn KH, Lee JH, Lee JH, Kim DY, Kang YA, Jeon M, Seol M, Ryu SG, Chung JW, Choi I, Lee KH. Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study. Bone Marrow Transplant. 2010 Jun;45(6):1038-46. doi: 10.1038/bmt.2009.304. Epub 2009 Nov 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence and severity of side effects of donor natural killer cell infusion		1 year	Yes
Secondary	anti-leukemia effect of donor natural killer cell infusion		2 years	No