Safety and Feasibility of the Use of Natural Killer Cells in Patients With Chronic Myeloid Leukemia

NCT ID: NCT03348033

Last Updated: 2019-03-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-31
• Study Completion Date: 2023-03-31

Brief Summary

The purpose of this study is to evaluate safety, feasibility and maximum tolerated dose of NK cells cultured in vitro as adjuvant treatment of patients with chronic myeloid leukemia candidates to allogenic bone marrow transplantation or refractory to conventional treatment.

Detailed Description

Natural killer (NK) cells are one of the main type of immune cells that mediate the graft-versus-leukemia (GVL) effect. They are a fundamental part of innate immunity, with a major role in rapid response against infectious agents and activating immune system against tumoral cells. Patients with chronic myelogenous leukemia (CML), however, seem to have lower NK cell counts as disease progresses from chronic phase to blast crisis, as well as diminished cytotoxicity in those NK cells remaining. Therapeutic role of the NK cell ability to target certain specific cells is currently being studied, especially regarding their action against tumoral cells. Chronic myeloid leukemia studies with NK cells have so far demonstrated that autologous ex vivo activated NK cells are able to suppress in vitro the presence of the breakpoint cluster region-abelson leukemia virus (BCR-ABL) oncogene. These studies have demonstrated that adoptive NK cell therapy may have a potential role in treatment of CML patients.

The purpose of this study is to evaluate safety, feasibility and maximum tolerated dose of NK cells cultured in vitro as adjuvant treatment of patients with chronic myeloid leukemia candidates to allogenic bone marrow transplantation or refractory to conventional treatment.

NK cells will be expanded from peripheral blood mononuclear cells after depletion of T cells. They ar going to be co-cultured with clone 9 K562 artificial antigen presenting cell (aAPCs), which are posteriorly modified to also express membrane interleukin-21 (mIL-21)

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chronic Myeloid Leukemia + NK cell

Starting on Day -7, G-CSF daily by vein until post nadir of absolute neutrophil counts (ANC) are equal or over 1000. Day -6 to Day -2 Fludarabine administrated by vein at 30 mg/m^2. Four hours later Cytarabine administrated by vein at 2 g/m^2. Natural killer (NK) cell infusion Days 0 to 14 for 6 doses total.

NK Cell infusion on Days 0 to 14 for 6 doses total.

Group Type: EXPERIMENTAL

Chronic Myeloid Leukemia + NK cell

Intervention Type: BIOLOGICAL

Patients with chronic phase chronic myeloid leukemia who lost response to the second line of treatment with tyrosine kinase inhibitor with indication of bone marrow transplantation or refractory. Infusion of autologous natural killer cells, expanded in the laboratory, after chemotherapeutic conditioning.

Interventions

Chronic Myeloid Leukemia + NK cell

Patients with chronic phase chronic myeloid leukemia who lost response to the second line of treatment with tyrosine kinase inhibitor with indication of bone marrow transplantation or refractory. Infusion of autologous natural killer cells, expanded in the laboratory, after chemotherapeutic conditioning.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients with chronic phase CML who lost response to the second line of treatment with tyrosine-kinase inhibitor (TKI) with indication for bone marrow transplantation.
• Accelerated phase patients who are candidates for bone marrow transplantation.
• Patient with CML in blast crisis.
• Patient aged between 2 and 59 years.
• patient should have recovered from the toxicity related to previous treatment of cytotoxic agents received within 4 weeks before starting treatment in this protocol, except for cytopenias resulting from persistent disease and alopecia, or non-haematological toxicities grades 1 and 2

Exclusion Criteria

• Zubrod performance scale ≥ 2
• Renal impairment: Serum creatinine> 2mg / dL for adults and> 2mg / dL or> 2 times the upper limit of normality for age (whichever is less) for children.
• Impaired hepatic function, defined as: total bilirubin> 2 mg / dL and alanine aminotransferase (ALT) 2.5 times upper limit of normal for age (unless Gilbert's disease or abnormal liver function due to primary disease).
• Pulmonary symptoms with pulse oximetry <92%.
• Congestive Heart Failure Classification New York Heart Association> III
• Positive serological test for pregnancy within two weeks prior to enrollment in women of childbearing potential (non-fertile age defined as pre-menarche, post-menopausal over one year, or surgically sterilized).
• Positive serology for human immunodeficiency virus (HIV).
• Have undergone investigational therapies in four weeks prior to treatment begin under this protocol.
• Congestive heart failure < 6 months prior to screening.
• Unstable angina < 6 months before screening.
• Myocardial infarction < 6 months prior to selection.
• Non-signing of the informed consent.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lucia Silla, Physician

Role: PRINCIPAL_INVESTIGATOR

Federal University of Rio Grande do Sul

Locations

Centro Terapia e Tecnologia Celular

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

Other Identifiers

160409

Identifier Type: -

Identifier Source: org_study_id