Granulocyte/ Polymorphonuclear Cells
Conditions
Brief summary
The purpose of this study is to compare the procedures for the collection PMN cells on Terumo BCT's Spectra Optia® and COBE® Spectra Apheresis Systems.
Detailed description
The purpose of this study is to compare the procedures for the collection of granulocyte/ polymorphonuclear (PMN) cells on Terumo BCT's Spectra Optia® and COBE® Spectra Apheresis Systems and to establish the non-inferiority of the Spectra Optia Apheresis System with respect to the primary study endpoint, granulocyte/PMN cell collection efficiency.
Interventions
DEVICEGranulocyte/Polymorphonuclear Cell Collection (COBE Spectra System)
In Arm 1 the first PMN cell collection will be performed using the Spectra Optia System and the second PMN cell collection using the COBE Spectra System.
DEVICEGranulocyte/Polymorphonuclear Cell Collection (Spectra Optia System)
In Arm 2 the first PMN cell collection will be performed using the COBE Spectra System and the second PMN cell collection using the Spectra Optia System.
Sponsors
Terumo BCT
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Acceptable health status and vital signs per the AABB blood donation guidelines to permit blood donation, including: 1. Blood pressure ≥ 90/50 and ≤ 200/120 mmHg, 2. Pulse \> 40 and \< 100 beats/min, and 3. Temperature \< 99.5ºFahrenheit (F). * Able to read, understand, and sign an English informed consent form. * Age ≥ 18 years. * Weight ≥ 50kg and \< 227kg. * Male or non-pregnant, non-nursing female (a negative serum pregnancy test at screening and a negative urine pregnancy test prior to each mobilization). * Acceptable screening laboratory test results prior to the first PMN cell mobilization, including: 1. WBC count in the range: 3,500-10,800/uL, 2. Hematocrit in the range: 38-65%, 3. Platelet count in the range: 150,000-400,000/uL, 4. Coagulation tests: PT not greater than 1.1 times the upper limit of the local laboratory reference range; PTT not greater than 1.2 times the upper limit of the local laboratory reference range, 5. Serum electrolyte concentrations: potassium in the range 3.6-5.1 mmol/L; calcium in the range 8.5-10.3 mg/dL, 6. Serum creatinine not greater than 1.5mg/dL, and 7. ALT not greater than 1.5 times the upper limit of the local laboratory reference range. \*\*\* Up to two (2) of the above screening laboratory test results may fall outside of these ranges, if in the judgment of the principal investigator or designee, they do not constitute a significant risk to the subject. Any excused deviations from the above will be listed and summarized with the final report.\*\*\* * Adequate dual peripheral venous access to allow collection of granulocytes (PMN cells) and return of remaining cells, platelets and plasma. * If male, willing to use a condom during sexual relations with a female partner of child bearing potential until 48 hours following each G-CSF injection. * If female, willing to use a medically-acceptable contraceptive until 48 hours following each G-CSF injection.
Exclusion criteria
* Positive screening for any of the following: HIV, HBV (except isolated HB core Ab reactivity), HCV, HTLV, Syphilis or West Nile Virus. * Currently pregnant or breast-feeding. * Collection or loss of specific volumes of whole blood or blood components during specified timeframes: 1. more than 550mL of whole blood within the prior 56 days, or 2. more than 3L of whole blood or 1.5L of red blood cells within the prior 12 months, or 3. more than 12L of plasma within the prior 12 months, or 4. a leukapheresis within the prior six weeks, or 5. a plateletpheresis within the prior 48 hours or two within the prior 7 days or twenty-four within the last 12 months, or 6. a plasmapheresis within the prior 48 hours or two within the prior 7 days. * History of congestive heart failure. * History of uncontrolled hypertension (SBP/DBP \>200/120 mmHg). * History or suspicion of active, peptic ulcer disease. * History of diabetes mellitus. * History of hematologic malignancy or chronic hematologic disorder. * Family history (parents, siblings, children) of hematologic malignancy. * History of deep vein thrombosis or venous thromboembolism, or bleeding disorder. * History of sickle cell disease or a positive SickleDex screen. * History of iritis or episcleritis. * History of autoimmune condition or disorder, unless approved by principal investigator. * Presence of psychological traits, or physiological or medical conditions that, in the opinion of the investigator, would make the subject unlikely to tolerate the procedures or complete the study. * History of use/anticipated need for lithium. * Received a G-CSF injection in the prior 4 months. * Known hypersensitivity to ethylene oxide. * Known hypersensitivity to G-CSF or hypersensitivity to any E. coli-derived products. * Known hypersensitivity to HES or corn. * Concurrent participation in another clinical trial or participation in a clinical trial within the past 30 days. * Subject is being treated with calcium channel blockers and/or antiepileptic medications. Note: This applies only to Subjects at Bonfils Blood Center whose collected product will undergo neutrophil function testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Granulocyte/PMN Cell Collection Efficiency | within 1 hour prior and within 5 minutes after each collection procedure | The primary endpoint is the granulocyte/PMN cell collection efficiency (CE) associated with the Granulocyte (PMN) Collection Procedures on the Spectra Optia and COBE Spectra Apheresis Systems. CE is a measurement of device performance calculated using donor and blood product blood counts collected immediately before and after the PMN collection procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of Blood Product - PMN Cell Yield | within 5 minutes after each collection procedure | Characterization of the collected blood product, specifically total PMN cell yield. This is a measurement of device performance measured by calculating cell counts in samples from the collected blood product. |
| Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed | within 5 minutes after each collection procedure | Characterization of the collected blood product, specifically PMN cell yield per liter blood processed. This is a measurement of device performance measured by calculating cell counts in samples from the collected blood product and blood processed measured by the device. |
| Characterization of the Blood Product - PMN Cell Viability | within 5 minutes after collection procedure | Characterization of the collected blood product, specifically PMN cell viability measured by an assay preformed on the collected blood product. |
| Characterization of the Blood Product - RBC Contamination | within 5 minutes after collection procedure | Characterization of the collected blood product, specifically red blood cell (RBC) contamination as measured by hematocrit in the collected PMN product. |
| Performance | within 1 hour prior and within 5 minutes after each collection procedure | Comparison of collection efficiencies associated with the Granulocyte Cell Collection Procedures on the Spectra Optia and COBE Spectra Apheresis Systems for white blood cells and platelets. CE is a measurement of device performance calculated using donor and blood product blood counts collected immediately before and after the collection procedure. |
| Usability/Assessment of System Operation - Time | Result captured immediately upon completion of procedure | Procedure time for collections on the Spectra Optia vs. the COBE Spectra. |
| Usability/Assessment of System Operation - Adjustments | Adjustments known immediately upon completion of the procedure | Number of operator adjustments aimed at establishing and maintaining the plasma/ cellular interface: namely, on Spectra Optia, the adjustment of collection preference and, on COBE Spectra, the adjustment of the plasma pump flow rate. |
| Usability/Assessment of System Operation - Device Malfunctions | Result know immediately upon successful completion of procedure | — |
| Safety | 48-hours after last procedure | * Serious adverse events (SAEs) and unanticipated (serious) adverse device/procedure- related events (UADEs), adverse events (AEs). * any clinically significant changes to Complete Blood Count with differential white cell count (CBCD) and any significant changes to vital signs (temperature, heart rate, blood pressure) were captured as AEs. Also provided in full report to FDA. |
| Characterization of the Blood Product - Volume | within 5 minutes after collection procedure | Characterization of the collected blood product, specifically product volume. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the specialized donor population of blood centers from February 2013 - July 2013.
Pre-assignment details
A screening period was used to evaluate and confirm eligibility criteria prior to enrollment & randomization to treatment assignment (Arm 1 or Arm 2). Fifty subjects consented to the pivotal study. Eight pivotal subjects consented but screen failed prior to treatment assignment. Forty-two received treatment assignment below.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 In Arm 1 the first PMN cell collection was performed using the Spectra Optia System and the second PMN cell collection using the COBE Spectra System for each subject. | 17 |
| Arm 2 In Arm 2 the first PMN cell collection was performed using the COBE Spectra System and the second PMN cell collection using the Spectra Optia System for each subject. | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Lead-in Donor Phase | screen failure | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Total |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 10.99 | 38.3 years STANDARD_DEVIATION 13.69 | 36.3 years STANDARD_DEVIATION 12.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 14 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 13 Participants | 29 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 48 | 11 / 42 |
| serious Total, serious adverse events | 0 / 48 | 0 / 42 |
Outcome results
Primary
Granulocyte/PMN Cell Collection Efficiency
The primary endpoint is the granulocyte/PMN cell collection efficiency (CE) associated with the Granulocyte (PMN) Collection Procedures on the Spectra Optia and COBE Spectra Apheresis Systems. CE is a measurement of device performance calculated using donor and blood product blood counts collected immediately before and after the PMN collection procedure.
Time frame: within 1 hour prior and within 5 minutes after each collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Granulocyte/PMN Cell Collection Efficiency | Spectra Optia CE% | 54.7 percent cells processed | Standard Deviation 6.46 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Granulocyte/PMN Cell Collection Efficiency | COBE Spectra CE% | 41.9 percent cells processed | Standard Deviation 6.14 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Granulocyte/PMN Cell Collection Efficiency | Spectra Optia CE% | 52.4 percent cells processed | Standard Deviation 7.43 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Granulocyte/PMN Cell Collection Efficiency | COBE Spectra CE% | 44.7 percent cells processed | Standard Deviation 6.18 |
Secondary
Characterization of Blood Product - PMN Cell Yield
Characterization of the collected blood product, specifically total PMN cell yield. This is a measurement of device performance measured by calculating cell counts in samples from the collected blood product.
Time frame: within 5 minutes after each collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of Blood Product - PMN Cell Yield | Spectra Optia PMN Cell Yield | 1.4 cells *10^10 | Standard Deviation 0.3 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of Blood Product - PMN Cell Yield | COBE Spectra PMN Cell Yield | 1.1 cells *10^10 | Standard Deviation 0.28 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of Blood Product - PMN Cell Yield | Spectra Optia PMN Cell Yield | 1.4 cells *10^10 | Standard Deviation 0.34 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of Blood Product - PMN Cell Yield | COBE Spectra PMN Cell Yield | 1.2 cells *10^10 | Standard Deviation 0.25 |
Secondary
Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed
Characterization of the collected blood product, specifically PMN cell yield per liter blood processed. This is a measurement of device performance measured by calculating cell counts in samples from the collected blood product and blood processed measured by the device.
Time frame: within 5 minutes after each collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed | Spectra Optia PMN Cell Yield per L of Blood Proces | 1.4 cells *10^10 per L of blood processed | Standard Deviation 0.3 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed | COBE Spectra PMN Cell Yield per L of Blood Proc | 1.1 cells *10^10 per L of blood processed | Standard Deviation 0.28 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed | Spectra Optia PMN Cell Yield per L of Blood Proces | 1.4 cells *10^10 per L of blood processed | Standard Deviation 0.34 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of Blood Product - PMN Cell Yield Per Liter of Blood Processed | COBE Spectra PMN Cell Yield per L of Blood Proc | 1.2 cells *10^10 per L of blood processed | Standard Deviation 0.25 |
Secondary
Characterization of the Blood Product - PMN Cell Viability
Characterization of the collected blood product, specifically PMN cell viability measured by an assay preformed on the collected blood product.
Time frame: within 5 minutes after collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - PMN Cell Viability | Spectra Optia PMN viability | 99.6 percent of viable cells | Standard Deviation 0.22 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - PMN Cell Viability | COBE Spectra PMN viability | 99.6 percent of viable cells | Standard Deviation 0.34 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of the Blood Product - PMN Cell Viability | Spectra Optia PMN viability | 99.6 percent of viable cells | Standard Deviation 0.28 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of the Blood Product - PMN Cell Viability | COBE Spectra PMN viability | 99.2 percent of viable cells | Standard Deviation 1.81 |
Secondary
Characterization of the Blood Product - RBC Contamination
Characterization of the collected blood product, specifically red blood cell (RBC) contamination as measured by hematocrit in the collected PMN product.
Time frame: within 5 minutes after collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - RBC Contamination | Spectra Optia Product HCT | 7.4 RBC percent of product volume | Standard Deviation 2.62 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - RBC Contamination | COBE Spectra Product HCT | 7.5 RBC percent of product volume | Standard Deviation 3.71 |
Secondary
Characterization of the Blood Product - Volume
Characterization of the collected blood product, specifically product volume.
Time frame: within 5 minutes after collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - Volume | Spectra Optia Product Volume | 472.6 mL | Standard Deviation 1.77 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Characterization of the Blood Product - Volume | COBE Spectra Product Volume | 329.7 mL | Standard Deviation 55.72 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of the Blood Product - Volume | Spectra Optia Product Volume | 471.9 mL | Standard Deviation 1.49 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Characterization of the Blood Product - Volume | COBE Spectra Product Volume | 298.5 mL | Standard Deviation 53.04 |
Secondary
Performance
Comparison of collection efficiencies associated with the Granulocyte Cell Collection Procedures on the Spectra Optia and COBE Spectra Apheresis Systems for white blood cells and platelets. CE is a measurement of device performance calculated using donor and blood product blood counts collected immediately before and after the collection procedure.
Time frame: within 1 hour prior and within 5 minutes after each collection procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Performance | Spectra Optia WBC CE% | 56.6 percent of cells processed | Standard Deviation 6.15 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Performance | COBE Spectra WBC CE% | 44.0 percent of cells processed | Standard Deviation 0.06 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Performance | Spectra Optia PLT CE% | 11.2 percent of cells processed | Standard Deviation 1.59 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Performance | COBE Spectra PLT CE% | 11.7 percent of cells processed | Standard Deviation 3.09 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Performance | COBE Spectra PLT CE% | 9.7 percent of cells processed | Standard Deviation 2.07 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Performance | Spectra Optia WBC CE% | 55.4 percent of cells processed | Standard Deviation 6.67 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Performance | Spectra Optia PLT CE% | 10.4 percent of cells processed | Standard Deviation 1.19 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Performance | COBE Spectra WBC CE% | 46.9 percent of cells processed | Standard Deviation 5.96 |
Secondary
Safety
* Serious adverse events (SAEs) and unanticipated (serious) adverse device/procedure- related events (UADEs), adverse events (AEs). * any clinically significant changes to Complete Blood Count with differential white cell count (CBCD) and any significant changes to vital signs (temperature, heart rate, blood pressure) were captured as AEs. Also provided in full report to FDA.
Time frame: 48-hours after last procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Safety | Number of subjects with >=1 AE | 17 events |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Safety | Spectra Optia SAEs | 0 events |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Safety | COBE Spectra SAEs | 0 events |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Safety | Spectra Optia UADEs | 0 events |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Safety | COBE Spectra UADEs | 0 events |
Secondary
Usability/Assessment of System Operation - Adjustments
Number of operator adjustments aimed at establishing and maintaining the plasma/ cellular interface: namely, on Spectra Optia, the adjustment of collection preference and, on COBE Spectra, the adjustment of the plasma pump flow rate.
Time frame: Adjustments known immediately upon completion of the procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Adjustments | Spectra Optia adjustments | 4.6 number of adjustments | Standard Deviation 2.12 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Adjustments | COBE Spectra adjustments | 9.3 number of adjustments | Standard Deviation 3.67 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Usability/Assessment of System Operation - Adjustments | Spectra Optia adjustments | 5.8 number of adjustments | Standard Deviation 2.48 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Usability/Assessment of System Operation - Adjustments | COBE Spectra adjustments | 10.7 number of adjustments | Standard Deviation 4.68 |
Secondary
Usability/Assessment of System Operation - Device Malfunctions
Time frame: Result know immediately upon successful completion of procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Device Malfunctions | Spectra Optia device deficiencies | 5 events |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Device Malfunctions | COBE Spectra device deficiencies | 0 events |
Secondary
Usability/Assessment of System Operation - Time
Procedure time for collections on the Spectra Optia vs. the COBE Spectra.
Time frame: Result captured immediately upon completion of procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Time | Spectra Optia Procedure Time | 136.8 minutes | Standard Deviation 20.78 |
| Arm 1 - Spectra Optia Followed by COBE Spectra | Usability/Assessment of System Operation - Time | COBE Spectra Procedure Time | 119.6 minutes | Standard Deviation 18.65 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Usability/Assessment of System Operation - Time | Spectra Optia Procedure Time | 120.3 minutes | Standard Deviation 17.58 |
| Arm 2 - COBE Spectra Followed by Spectra Optia | Usability/Assessment of System Operation - Time | COBE Spectra Procedure Time | 112.3 minutes | Standard Deviation 19.83 |