B-cell Acute Lymphoblastic Leukemia Clinical Trial
Official title:
Pilot Study of Redirected Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
Verified date | April 2019 |
Source | National University Health System, Singapore |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Modern therapy for patients with B-lineage acute lymphoblastic leukemia (ALL) is based on
intensive administration of multiple drugs. In patients with relapsed disease, treatment
response is generally poor; for most patients, particularly those who relapse while still
receiving frontline therapy, the only therapeutic option is hematopoietic stem cell
transplantation (HSCT). There is no proven curative therapy for patients who relapse after
transplant.
Natural killer (NK) cells have powerful anti-leukemia activity. In patients undergoing
allogeneic HSCT, several studies have demonstrated NK-mediated anti-leukemic activity. NK
cell infusions in patients with leukemia have been shown to be well tolerated and void of
graft-versus-host disease (GVHD) effects.
NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas
their capacity to lyse ALL cells is generally low. We have developed a novel method to expand
and 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 the cell line K562-mb15-41BBL and interleukin
(IL)-2. 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 will assess the feasibility, safety and efficacy of infusing expanded, activated
redirected NK cells into research participants with B-lineage ALL who have persistent disease
after intensive chemotherapy . In this same cohort, we will study the in vivo lifespan and
phenotype of these redirected NK cells.
Status | Suspended |
Enrollment | 20 |
Est. completion date | February 2020 |
Est. primary completion date | February 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 80 Years |
Eligibility |
Inclusion Criteria: - NK cell RECIPIENT: 1. Age: 0 months to 80 years old. 2. Patients with B-lineage ALL who have persistent disease (0.01% to less than 1% as determined by flow cytometric or molecular measurements of residual disease) despite intensive standard chemotherapy . 3. Shortening fraction greater than or equal to 25%. 4. Glomerular filtration rate greater than or equal to 50 ml/min/1.73 m2. 5. Pulse oximetry greater than or equal to 92% on room air. 6. Direct bilirubin less than or equal to 3.0 mg/dL (50 mmol/L). 7. Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal. 8. Aspartate transaminases (AST)is no more than 2 times the upper limit of normal. 9. Karnofsky or Lansky performance score of greater than or equal to 50. 10. No known allergy to murine products or HAMA testing results within normal limits. 11. No prior receipt of a gene-transfer agent (e.g. retroviral,adenoviral, lentiviral vector). 12. Does not have a current pleural or pericardial effusion. 13. Has a suitable adult family member donor available for NK cell donation. 14. Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the PI. 15. At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy. 16. Is not receiving more than the equivalent of prednisone 10 mg daily. 17. Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment). 18. Not lactating. - NK cell DONOR: 1. First and second relative acceptable. 2. 18 years of age or above. 3. Not lactating. 4. Greater than or equal to 3 of 6 HLA match to recipient. 5. Meets eligibility and suitability criteria for hematopoietic cells donation as per institutional guidelines. 6. Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment). Exclusion Criteria: - Failure to meet any of the inclusion criteria. |
Country | Name | City | State |
---|---|---|---|
Singapore | Department of Paediatrics, National University Health System | Singapore |
Lead Sponsor | Collaborator |
---|---|
National University Health System, Singapore |
Singapore,
Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, Eldridge P, Leung WH, Campana D. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009 May 1;69(9):4010-7. doi: 10.1158/0008-5472.CAN-08-3712. Epub 2009 Apr 21. — View Citation
Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005 Jul 1;106(1):376-83. Epub 2005 Mar 8. — View Citation
Lapteva N, Durett AG, Sun J, Rollins LA, Huye LL, Fang J, Dandekar V, Mei Z, Jackson K, Vera J, Ando J, Ngo MC, Coustan-Smith E, Campana D, Szmania S, Garg T, Moreno-Bost A, Vanrhee F, Gee AP, Rooney CM. Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications. Cytotherapy. 2012 Oct;14(9):1131-43. doi: 10.3109/14653249.2012.700767. Epub 2012 Aug 17. — View Citation
Shimasaki N, Fujisaki H, Cho D, Masselli M, Lockey T, Eldridge P, Leung W, Campana D. A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies. Cytotherapy. 2012 Aug;14(7):830-40. doi: 10.3109/14653249.2012.671519. Epub 2012 Mar 29. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Disease Response Criteria - Minimal Disease Residual (MRD) Monitoring | Treatment response will be measured by comparing MRD levels before and 1 month after NK cell infusion. Achievement of MRD negativity in bone marrow, i.e., < 0.01% blasts by flow cytometry or PCR, will be regarded as a complete response. Partial response will be defined as = 1 log decrease in MRD levels, while < 1 log decrease in MRD levels will be regarded as no response. | 1 Month Post NK Cell Infusion |
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