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

Primary Purpose

Lymphoblastic Leukemia, Acute

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NK Cell Infusion
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia, Acute focused on measuring Relapsed or refractory B-Lineage ALL

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

relapse B-Lineage ALL

Arm Description

All patients meeting the eligibility criteria. Intervention: NK Cell Infusion

Outcomes

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

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.
This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.

Full Information

First Posted
October 14, 2009
Last Updated
April 24, 2017
Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI), Assisi Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00995137
Brief Title
Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
Official Title
Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI), Assisi Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Acute
Keywords
Relapsed or refractory B-Lineage ALL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
relapse B-Lineage ALL
Arm Type
Experimental
Arm Description
All patients meeting the eligibility criteria. Intervention: NK Cell Infusion
Intervention Type
Biological
Intervention Name(s)
NK Cell Infusion
Intervention Description
Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Shook, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-3678
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28054442
Citation
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.
Results Reference
derived
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude

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

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