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

NCT ID: NCT00995137

Last Updated: 2017-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-05-31

Brief 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).

Detailed 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.

Conditions

Lymphoblastic Leukemia, Acute

Study Design

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

Study Groups

relapse B-Lineage ALL

All patients meeting the eligibility criteria.

Intervention: NK Cell Infusion

Group Type: EXPERIMENTAL

NK Cell Infusion

Intervention Type: BIOLOGICAL

Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.

Interventions

NK Cell Infusion

Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Assisi Foundation

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Shook, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

References

Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.

Reference Type: DERIVED

PMID: 28054442 (View on PubMed)

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

R01CA113482

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01226

Identifier Type: REGISTRY

Identifier Source: secondary_id

NKCD19

Identifier Type: -

Identifier Source: org_study_id