SPECTRA OPTIA
Report
- Report Number
- 1722028-2020-00179
- Event Type
- Malfunction
- Date Received
- April 21, 2020
- Date of Event
- March 24, 2019
- Report Date
- April 21, 2020
- Manufacturer
- TERUMO BCT
- Product Code
- GKT
- UDI-DI
- 05020583103108
- PMA / PMN Number
- K183081
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- SP
- Reporter Occupation
- PHYSICIAN
- Health Professional
- Yes
Narratives
THIS REPORT IS BEING FILED TO PROVIDE ADDITIONAL INFORMATION IN B.5, E.1, H.6 AND H.10 INVESTIGATION: SINCE THIS WAS A PROSPECTIVE STUDY CONDUCTED BETWEEN NOVEMBER 2017 AND APRIL 2018 THE LOT NUMBERS WERE NOT PROVIDED OR REQUESTED; THEREFORE, A DHR SEARCH COULD NOT BE CONDUCTED FOR THIS SPECIFIC INCIDENT. ALL LOTS MUST MEET ACCEPTANCE CRITERIA FOR RELEASE. THE OBJECTIVE OF THIS STUDY WAS TO PROVIDE EFFICIENCY AND PRODUCTIVITY DATA OBTAINED IN THE MANUFACTURED CELLULAR PRODUCTS INFUSED. NK CELLS PROVIDE A POTENT ANTITUMOR EFFECT IN THE SETTING OF MANIPULATED HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANT (HAPLO-HSCT). THE AUTHORS PROPOSE A NOVEL STRATEGY TO ENHANCE THE ANTITUMOR EFFECT OF ALLOGENEIC TRANSPLANT THROUGH THE INFUSION OF NK CELLS STIMULATED WITH IL-15 EX VIVO IN ADULT HIGH-RISK ACUTE MYELOID LEUKEMIA (AML) PATIENTS UNDERGOING UNMANIPULATED HAPLO-HSCT. METHODS: SELECTION CRITERIA INCLUDED PATIENTS WITH HIGHRISK AML UNDERGOING UNMANIPULATED HAPLO-HSCT. LYMPHOAPHERESIS OF THE HAPLOIDENTICAL DONOR WAS PERFORMED USING SPECTRA OPTIA (TERUMO® BCT) ON DAYS +6 AND +13 AFTER TRANSPLANT. FROM THE OBTAINED PRODUCT A DOUBLE IMMUNOMAGNETIC CELLULAR SELECTION WITH CLINIMACS SYSTEM (MILTENYI BIOTEC®) WAS PERFORMED IN TWO STEPS: CD3+ DEPLETION FOLLOWED BY POSITIVE CD56+ SELECTION. THE OBTAINED AN ENRICHED CELLULAR PRODUCT OF CD3-CD56+ NK CELLS WAS INCUBATED WITH IL-15 (10 NG/ML) BETWEEN 12 AND 18 HOURS AT 37ºC AND 5% CO2 IN GMP CONDITIONS. QUALITY AND MICROBIOLOGICAL CONTROLS WERE PERFORMED AT THE END OF EACH MANUFACTURING STEP. DXH CELLULAR COUNTERS (BECKMAN COULTER®) AND MULTIPARAMETRIC FLOW CYTOMETRY WERE USED FOR LYMPHOCYTE SUBPOPULATIONS AND VIABILITY ANALYSIS (NAVIOS CYTOMETER; BECKMAN COULTER®, CONJUGATED MONOCLONAL ANTIBODIES; MILTENYI BIOTEC®). THE FINAL PRODUCT WAS INFUSED INTRAVENOUSLY TO THE PATIENT ON DAYS +8 AND +15 IF MANUFACTURING CONDITIONS WERE MET (RANGE OF 0.5-100X106 NK/KG, PURITY = 80%, VIABILITY= 70% AND < 1X104 CD3+ CELLS/KG). IF NOT, IT WAS DISCARDED. NK CELL ACTIVATION IN THE PRODUCT WAS MEASURED BY THE EXPRESSION OF CD25 AND CD69. RESULTS: BETWEEN NOVEMBER 2017 AND APRIL 2018, 3 PATIENTS WERE INCLUDED IN THIS ONGOING TRIAL. TWO PRODUCTS WERE MANUFACTURED FOR 2 OF THE PATIENTS, AND ONLY ONE FOR THE FIRST PATIENT, DUE TO TRANSPLANT COMPLICATIONS BETWEEN FIRST AND SECOND INFUSION. ONE PRODUCT DID NOT MEET MINIMUM VIABILITY CRITERIA AND WAS DISCARDED. IN THE INFUSED FINAL PRODUCTS MEAN AND SEM OF NK CELL PURITY, RECOVERY AND VIABILITY WERE 83.7%±4.4, 30.9%±4 AND 76.3%±17.4, RESPECTIVELY. LOG CD3+ DEPLETION RANGED BETWEEN -5.48 AND -6.03. MEDIAN INFUSED DOSES OF NK CELLS AND CD3+ CELLS PER KG WERE 3.78X106(2.8X106-4.57X106) AND 114 (87- 532). COMPLETE MANUFACTURING DATA OF ALL 5 PROCEDURES ARE SHOWN IN TABLE 1. MEAN EXPRESSION OF ACTIVATION MARKERS WAS: CD69 (BASAL 15.6%± 2.6, AFTER IL-15 69%±12.7), CD25 (BASAL 0.1%±0.04, IL-15 33%±7.75). NO PATIENT HAD IMMEDIATE ADVERSE EFFECTS WITH PRODUCT INFUSION. CONCLUSIONS: WE DEMONSTRATE THE FEASIBILITY OF THE MANUFACTURING PROCESS OF IL-15 STIMULATED NK CELLS FROM HAPLOIDENTICAL DONORS AND EARLY POST-TRANSPLANT INFUSION IN ADULT AML PATIENTS IN THE SETTING OF UNMANIPULATED HAPLO-HSCT. ACHIEVED DOSES OF NK CELLS FOR ADULT PATIENTS ARE PROMISING, WITH SAFE CONTENT OF CONTAMINANT T LYMPHOCYTES LESS THAN 1X104 /KG. MORE PROCEDURES NEED TO BE ANALYZED IN ORDER TO CONFIRM THIS OBSERVATION. PER LITERATURE REVIEW (KAZUHIKO IKEDA, ET AL REPORTED ON 1125 HSCTS, INCLUDING 570 PERIPHERAL BLOOD STEM CELL TRANSPLANTATIONS (PBSCTS) (290 AUTOLOGOUS [AUTO-] AND 280 ALLOGENEIC [ALLO-]), 332 ALLO-BONE MARROW TRANSPLANTATIONS (ALLO-BMTS) AND 223 ALLO-CORD BLOOD TRANSPLANTATIONS (ALLO-CBTS). UNEXPECTEDLY, INCIDENCES OF GRADE = 2AES WERE MOST FREQUENT IN ALLO-BMTS (37.7%) WITH NO DMSO IN ANY PRODUCT COMPARED WITH AUTO-/ALLO PBSCTS (20.9%, P < .001) AND ALLO-CBTS (19.3%, P < .001) TYPICALLY CRYOPRESERVED WITH DMSO. HYPERTENSION WAS MOST OFTEN NOTED IN BMTS, WHEREAS NAUSEA/VOMITING, FEVER, AND ALLERGIC REACTIONS WERE MOST FREQUENT IN ALLO-PBSCTS. IN A MULTIVARIATE ANALYSIS, A HISTORY OF TRANSFUSION REACTIONS WAS A RISK FACTOR FOR OVERALL AES IN ALL HSCTS (ODDS RATIO [OR]=1.459, P=.045). FOR GRADE = 2 AES IN ALLO-HSCTS, A HISTORY OF TRANSFUSION REACTIONS (OR=1.551, P=.044) FOR OVERALL AES, AND HIGH INFUSION VOLUME (OR=7.544, P=.005) AND ALLO-PBSCTS (VERSUS BMTS, OR=9.948, P=.002) FOR ALLERGIC REACTIONS WERE IDENTIFIED AS RISK FACTORS. THESE FINDINGS SUGGEST THAT SOME FACTORS UNRELATED TO DMSO, SUCH AS ALLO-ANTIGENS, CONTRIBUTE TO HSC INFUSION-RELATED AES ROOT CAUSE: A DEFINITIVE ROOT CAUSE FOR THE PATIENTS' REACTION COULD NOT BE DETERMINED. POSSIBLE CAUSES FOR THE TRANSPLANT COMPLICATIONS INCLUDE BUT ARE NOT LIMITED TO THE PATIENT'S DISEASE STATE, GRAFT-VERSUS-HOST DISEASE, STEM CELL (GRAFT) FAILURE, AND/OR CONDITIONING REGIMENT. POSSIBLE CAUSES FOR LOW VIABILITY INCLUDE BUT ARE NOT LIMITED TO: - ISSUES RELATED TO CRYOPRESERVATION TECHNIQUE/PROCESS - IMPROPER STORAGE CONDITIONS - IMPROPER FREEZING AND THAWING TECHNIQUE.
PURSUANT TO EUROPEAN PERSONAL DATA PROTECTION LAWS, THE PATIENT INFORMATION IS NOT AVAILABLE.
INVESTIGATION: LOT NUMBER AND EXPIRY INFORMATION ARE NOT AVAILABLE AT THIS TIME. CITATION: "THE 45TH ANNUAL MEETING OF THE EUROPEAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION: PHYSICIANS ¿ POSTER SESSION." BONE MARROW TRANSPLANTATION, VOL. 54, NO. S1, 2019, PP. 144¿619., DOI:10.1038/S41409-019-0559-4. INVESTIGATION IS IN PROCESS. A FOLLOW-UP REPORT WILL BE PROVIDED.
PER THE MEETING ABSTRACTS FOR "THE 45TH ANNUAL MEETING OF THE EUROPEAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION: PHYSICIANS ¿ POSTER SESSION" IT WAS DETERMINED THAT THE SPECTRA OPTIA FOR LYMPHOPHERESIS OF HAPLOIDENTICAL DONORS TO PRODUCE CELL PRODUCTS FOR HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANT IN PATIENTS WITH HIGH RISK ACUTE MYELOID LEUKEMIA. THE AUTHORS NOTE THAT 5 PRODUCTS WERE MANUFACTURED AND THAT 1 OF THESE PRODUCTS DID NOT MEET MINIMUM VIABILITY CRITERIA AND WAS DISCARDED. FROM THE OBTAINED PRODUCT A DOUBLE IMMUNOMAGNETIC CELLULAR SELECTION WITH CLINIMACS SYSTEM (MILTENYI BIOTEC - NOT A TBCT PRODUCT) WAS PERFORMED IN TWO STEPS: CD3+ DEPLETION FOLLOWED BY POSITIVE CD56+ SELECTION. THE ENRICHED CELLULAR PRODUCT OF CD3-CD56+ NK CELLS WAS INCUBATED WITH IL-15 (10 NG/ML) BETWEEN 12 AND 18 HOURS AT 37ºC AND 5% CO2 IN GMP CONDITIONS. THE FINAL PRODUCT WAS INFUSED INTRAVENOUSLY TO THE PATIENT ON DAYS +8 AND +15 IF MANUFACTURING CONDITIONS WERE MET (RANGE OF 0.5-100X106 NK/KG, PURITY = 80%, VIABILITY= 70% AND < 1X104 CD3+ CELLS/KG). BETWEEN NOVEMBER 2017 AND APRIL 2018, 3 PATIENTS WERE INCLUDED IN THIS ONGOING TRIAL. TWO PRODUCTS WERE MANUFACTURED FOR 2 OF THE PATIENTS, AND ONLY ONE FOR THE FIRST PATIENT, DUE TO TRANSPLANT COMPLICATIONS BETWEEN FIRST AND SECOND INFUSION. ONE PRODUCT DID NOT MEET MINIMUM VIABILITY CRITERIA AND WAS DISCARDED. SPECIFIC DETAILS, INCLUDING PATIENT INFORMATION AND OUTCOME WERE NOT PROVIDED IN THE ARTICLE, THEREFORE, THIS REPORT IS BEING PROVIDED AS A SUMMARY OF THE ADVERSE EVENTS. THE DISPOSABLE SET IS NOT AVAILABLE FOR RETURN BECAUSE IT WAS DISCARDED BY THE CUSTOMER.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 448059 | SPECTRA OPTIA | SPECTRA OPTIA IDL SET | GKT | TERUMO BCT | 10310 | 05020583103108 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | Unknown | Other |