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

NCT03348033 | Unknown Phase 1

• 1 other identifier: 160409
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of membrane-bound interleukin 21 (mbIL21)-Expanded Haploidentical NK Cells After Induction Chemotherapy with Fludarabine, Cytarabine, and Granulocyte-colony stimulating factor (G-CSF)

  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

  28 days

Secondary Outcomes (1)

• Molecular response Assessment Following Infusion of the NK Cells

  Baseline up to Day 56

Study Arms (1)

Chronic Myeloid Leukemia + NK cell

EXPERIMENTAL

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.

Biological: Chronic Myeloid Leukemia + NK cell

Interventions

Chronic Myeloid Leukemia + NK cell 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.

Chronic Myeloid Leukemia + NK cell

Eligibility Criteria

• Age: 2 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead

Study Sites (1)

Centro Terapia e Tecnologia Celular

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lucia Silla, Physician

  Federal University of Rio Grande do Sul

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: November 20, 2017
• Study Start: March 1, 2019
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2023
• Last Updated: March 12, 2019

Record last verified: 2019-02

Locations

BR (1)