Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
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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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 18 |
| Study Start Date: | October 2009 |
| Estimated Study Completion Date: | October 2013 |
| Estimated Primary Completion Date: | October 2013 (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 |
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)
- Lactating
Contacts and Locations| Contact: David Shook, MD | 1-866-278-5833 | info@stjude.org |
| United States, Tennessee | |
| St Jude Children's Research Hospital | Recruiting |
| Memphis, Tennessee, United States, 38105-3678 | |
| Contact: David Shook, MD 866-278-5833 info@stjude.org | |
| 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, CA113482 |
| Study First Received: | October 14, 2009 |
| Last Updated: | November 29, 2012 |
| 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 May 22, 2013