Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia

Lymphoblastic Leukemia, Acute Clinical Trial

Official title:

Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995137
• Other study ID #: NKCD19
• Secondary ID: R01CA113482NCI-2
• Status: Completed
• Phase: Phase 1
• First received: October 14, 2009
• Last updated: April 24, 2017
• Start date: October 2009
• Est. completion date: May 2014

Study information

• Verified date: February 2015
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine the maximum tolerated dose of genetically modified natural killer (NK) cells in research participants with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL).

Description:

NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas their capacity to lyse ALL cells is generally low and difficult to predict. A novel method has been developed to redirect NK cells towards CD19, a molecule highly expressed on the surface of B-lineage ALL cells, but not expressed on normal cells other than B-lymphocytes. In this method, donor NK cells are first expanded by co-culture with irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Overexpansion of these proteins promotes selective growth of NK cells. Then, the expanded NK cells are transduced with a signaling receptor that binds to CD19 (anti-CD19-BB-zeta). NK cells expressing these receptors showed powerful anti-leukemic activity against CD19+ ALL cells in vitro and in an animal model of leukemia.

This study represents the translation of laboratory findings into clinical application. It will allow us to assess the safety of infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL. In this same cohort, we also intend to study the in vivo lifespan and phenotype of genetically modified NK cells and explore the efficacy of NK cells in patients with B-lineage ALL.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: May 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Age: less than or equal to 18 years of age. May be greater than 18 years of age if currently a St. Jude patient.

• Patients with relapsed or refractory B-lineage ALL who are not eligible for hematopoietic stem cell transplantation (HSCT) because their leukemia is not in remission (>5% blasts in bone marrow as evidenced either by morphology or by flow cytometry).

• Shortening fraction greater than or equal to 25%.

• Glomerular filtration rate greater than or equal to 50 cc/min/1.73 m2.

• Pulse oximetry greater than or equal to 92% on room air.

• Direct bilirubin less than or equal to 3.0 mg/dL.

• Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.

• Aspartate transaminases (AST) is no more than 2 times the upper limit of normal.

• Karnofsky or Lansky performance score of greater than or equal to 50.

• No known allergy to murine products or HAMA testing results within normal limits.

• No prior receipt of a gene-transfer agent (e.g. retroviral, adenoviral, lentiviral vector).

• Does not have a current pleural or pericardial effusion.

• Has a suitable adult family member donor available for NK cell donation.

• Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from previous therapy as per the judgment of the principal investigator.

• At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.

• Is not receiving more than the equivalent of prednisone 10 mg daily.

Exclusion Criteria:

• Pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment)

• Breastfeeding

Related Conditions & MeSH terms

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

Intervention

Biological:
• NK Cell Infusion
Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.

Locations

Country	Name	City	State
United States	St Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	Assisi Foundation, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL		30 days after the enrollment of the last patient
Secondary	This study will determine the persistence and phenotype of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.		30 days after the enrollment of the last patient
Secondary	This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.		30 days after the enrollment of the last patient

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital