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

April 24, 2017 updated by: St. Jude Children's Research Hospital

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105-3678
        • St Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: relapse B-Lineage ALL

All patients meeting the eligibility criteria.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
30 days after the enrollment of the last patient

Secondary Outcome Measures

Outcome Measure
Time Frame
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
30 days after the enrollment of the last patient
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
30 days after the enrollment of the last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

National Cancer Institute (NCI)
Assisi Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (ACTUAL)

May 1, 2013

Study Completion (ACTUAL)

May 1, 2014

Study Registration Dates

First Submitted

October 14, 2009

First Submitted That Met QC Criteria

October 14, 2009

First Posted (ESTIMATE)

October 15, 2009

Study Record Updates

Last Update Posted (ACTUAL)

April 26, 2017

Last Update Submitted That Met QC Criteria

April 24, 2017

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKCD19
  • R01CA113482 (U.S. NIH Grant/Contract)
  • NCI-2011-01226 (REGISTRY: NCI Clinical Trial Registration Program)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoblastic Leukemia, Acute

Clinical Trials on NK Cell Infusion

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe