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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00995137
First received: October 14, 2009
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Lymphoblastic Leukemia, Acute
Genetic: NK Cell Infusion
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL [ Time Frame: 30 days after the enrollment of the last patient ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • This study will determine the persistence and phenotype of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL. [ Time Frame: 30 days after the enrollment of the last patient ] [ Designated as safety issue: Yes ]
  • This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL. [ Time Frame: 30 days after the enrollment of the last patient ] [ Designated as safety issue: Yes ]

Enrollment: 14
Study Start Date: October 2009
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: relapse B-Lineage ALL

All patients meeting the eligibility criteria.

Intervention: NK Cell Infusion

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

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00995137

Locations
United States, Tennessee
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105-3678
Sponsors and Collaborators
St. Jude Children's Research Hospital
Assisi Foundation
Investigators
Principal Investigator: David Shook, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00995137     History of Changes
Other Study ID Numbers: NKCD19, R01CA113482
Study First Received: October 14, 2009
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Relapsed or refractory B-Lineage ALL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on April 23, 2014