Neoplasms

Blood and Lymph Conditions

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Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cytarabine

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Tyrosine Kinase Inhibitors

Tyrosine

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.

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.

Chronic Myeloid Leukemia + NK cell

Lucia Silla, Physician

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.

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)

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

Adoptive Immunotherapy in Patients With Chronic Myeloid Leukemia: Phase I/II Study to Test the Safety and Feasibility of Autologous Activated and Expanded Natural Killer Cells

Maximum tolerated dose defined as highest dose studied in which 6 patients have been treated and at most 2 patients with dose-limiting toxicities (DLTs) observed.

A dose-limiting toxicity (DLT) is defined as:

Acute severe (grade 3 or 4) infusional allergic reaction related to the NK cells infusion.

Prolonged cytopenia beyond D+28. If neutropenia is still present at day 28, that will trigger the designation of prolonged neutropenia as a DLT. If neutrophil counts have recovered by day 28, then no DLT will have occurred. In either case, the status of neutrophil recovery beyond day 28 will not change the designation of DLT or No DLT made at day 28.

Acute graft-versus-host disease (GvHD) overall grade 3 or 4. Severe (grade 3 or 4) unexpected toxicity related to the NK cell infusion

Percentage of participants with major molecular response - amount of BCR-ABL gene in the blood is 1/1000th (or less) of what is expected in someone with untreated CML.

Hospital de Clinicas de Porto Alegre

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Feasibility of the Use of Natural Killer Cells in Patients With Chronic Myeloid Leukemia	NCT03348033	Chronic Myeloid...	Chronic Myeloid...	2 Years - 59 Years	Hospital de Clinicas de Porto Alegre
Safety and Feasibility of the Use of Natural Killer Cells in Patients With Chronic Myeloid Leukemia	NCT03348033	Chronic Myeloid...	Chronic Myeloid...	2 Years - 59 Years	Hospital de Clinicas de Porto Alegre

Spots Global Cancer Trial Database for chronic myeloid leukemia + nk cell