Randomized Study of Haploidentical Hct and Subsequent Donor nk Cell Infusion in High-risk AML and MDS

NCT02477787 | Terminated Phase 2 DMC

• 1 other identifier: 2014-1091
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open label, random comparison phase 2b study. The primary objective of this study is, by random comparison, to assess the anti-leukemia effect of allogeneic, donor-derived natural killer (NK) cells infused after HLA-haploidentical hematopoietic cell transplantation (HCT) in patients with refractory acute myelogenous leukemia (AML). The secondary objectives of the study are to assess the side effects of donor NK cell infusion, effects of donor NK cell infusion upon HCT outcomes, as well as effects upon post-HCT immune recovery.

Conditions

Acute Myelogenous Leukemia

Keywords

HLA-haploidentical hematopoietic cell transplantation; natural killer cells

Outcome Measures

Primary Outcomes (1)

• number of patients who experience progression/recurrence of AML after HCT

  up to 60 months

Secondary Outcomes (5)

• number of patients who achieve engraftment after HCT

  up to 6 months

• number of patients who develop acute GVHD

  up to 4 months

• number of patients who develop chronic GVHD

  up to 60 months

• number of patients who experience donor NK cell infusion-associated toxicity

  up to 1 month

• number of patients who die after HCT without progression of AML

  up to 60 months

Study Arms (2)

treatment

EXPERIMENTAL

patients will receive donor-derived NK cell infusion after haploidentical HCT

Biological: allogeneic, donor-derived NK cells

control

NO INTERVENTION

patients will undergo haploidentical HCT but not receive donor-derived NK cells after HCT

Interventions

allogeneic, donor-derived NK cells BIOLOGICAL

Patients in the study arm will receive donor NK cell infusion around days 13 and 20. A permissible range of infusion time will be +/- 3 days. For DNKI to be given on day 13 (DNKI-1), the cell dose is 1-2 x108/kg or about the half of amount generated. For DNKI to be given on day 20 (DNKI-2), the cell dose is up to 5x108/kg. Avil 1 ampoule will be given intravenously 30 minutes prior to each NK cell infusions.

treatment

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with refractory AML Refractory AML is defined as follows;
• Primary refractory: failure to achieve complete remission (CR) after 2 cycles of induction chemotherapy; or, in patient ≥65 years of age, progressive AML after treatment with hypomethylating agent (increase in peripheral blood blast by 50% or increase in bone marrow blast by 25%)
• Relapse then refractory: recurrence of AML, which is refractory to standard salvage chemo therapy; or, in patient ≥65 years of age, to hypomethylating agent
• AML in ≥2 relapses
• Patients should be 19 years of age or older
• Patients should have Karnofsky performance scale ≥70
• Patients and cell donors must understand fully and sign informed consent forms

You may not qualify if:

• Pregnant or lactating women
• Patient with abnormal liver function (total bilirubin ≥ 5.0 mg/dl, AST ≥ 5 times upper normal limits)
• Patients with abnormal renal function (creatinine ≥ 3.0 mg/dl)
• Patients with clinically-evident cardiac or pulmonary dysfunction
• Patients with infection that is progressive despite appropriate anti-microbial treatment
• Patients with hypersensitivity to gentamicin
• Patients who had received allogeneic cell therapy previously.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, South Korea

Location

Related Publications (1)

• Lee KH, Yoon SR, Gong JR, Choi EJ, Kim HS, Park CJ, Yun SC, Park SY, Jung SJ, Kim H, Lee SY, Jung H, Byun JE, Kim M, Kim SY, Kim JH, Lee JH, Lee JH, Choi Y, Park HS, Lee YS, Kang YA, Jeon M, Woo J, Kang H, Baek S, Kim SM, Kim HM, Cho KH, Choi I. The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients-a randomized trial. Leukemia. 2023 Apr;37(4):807-819. doi: 10.1038/s41375-023-01849-5. Epub 2023 Mar 17.

  PMID: 36932165 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PROFESSOR, HEMATOLOGY

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 23, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 8, 2019

Record last verified: 2019-07

Locations

KR (1)