Evaluation of the Spectra Optia® Mononuclear Cell Collection Procedure

Study Overview
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Brief Summary
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The purpose of this investigation is to establish that hematopoetic stem cells collected on a new centrifugal blood separator, CaridianBCT's Spectra Optia Apheresis System, are able to reconstitute the hematopoetic systems of patients treated with myeloablative therapy, equivalent to hematopoetic cells harvested on the predicate COBE® Spectra platform.

Detailed Description
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This is a multi-center (3-5) single-arm study that will compare the performance of the Spectra Optia Apheresis System's MNC protocol to that of the historical performance of the COBE Spectra MNC protocol. In order to demonstrate the substantial equivalence of the two devices, a non-inferiority design will be used. The study will enroll patients with multiple myeloma who are to be treated with myeloablative chemotherapy, followed by bone-marrow rescue with an autologous peripheral blood stem-cell transplant. Peripheral blood stem cells will be collected using the Spectra Optia MNC protocol and re-infused following myeloablative chemotherapy.

Official Title
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Evaluation of the Spectra Optia® Apheresis System Mononuclear Cell (MNC) Collection Procedure in Multiple Myeloma Patients

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Device: Spectra Optia Apheresis System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic confirmation of Multiple Myeloma Patients intended to be treated with myeloablative therapy and autologous hematopoetic stem-cell transplant within one month of stem-cell collection Patients whose stem-cell mobilization regimen includes G-CSF (granulocyte-colony stimulating factor) Males or non-pregnant females, who are 18 years of age or older Karnofsky score of ≥70% Exclusion Criteria: Patients with pre-mobilization platelet count < 75,000/µL Patients who have received pelvic bone marrow irradiation as part of their conditioning therapy Patients who have had a previous hematopoetic stem-cell transplant Patients who have had a previous hematopoetic stem-cell collection failure Impaired cardiac function, as evidenced by left ventricular ejection fraction <40%. Impaired hepatic function, as evidenced by alanine transaminase >2.5 x normal Impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (adjusted for patient hematocrit, if indicated) or forced expiratory volume in 1 second <50% of predicted Impaired renal function, as evidenced by a creatinine clearance < 40 mL/min Impaired coagulation, as evidenced by a prothrombin time (PT) > twice normal Pregnancy or lactation Seropositivity for Human Immunodeficiency Virus-1/2, Hepatitis B Virus, or Hepatitis C Virus Documented bacterial or fungal infection that requires intravenous antibiotics to be started or continued while undergoing apheresis collection on the Spectra Optia device Subjects enrolled in study protocols that could affect number of CD34+ cells (pluripoten hematopoetic stem stells) collected or kinetics of neutrophil recovery Altered mental status, as evidenced by the inability to provide effective informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with multiple myeloma<br>Multiple myeloma patients who receive autologous stem-cell transplants, collected using the Spectra Optia Apheresis System, following myeloablative therapy. The study is limited to subjects who are expected demonstrate normal neutrophil recovery. | Device: Spectra Optia Apheresis System<br>* In this study, the safety and effectiveness of the new device will be assessed in two ways. First, MNC collections in growth-factor mobilized cancer patients will be evaluated to confirm that the Spectra Optia is able to collect stem cells. Second, following stem-cell collection and transplant, the number of days required for the collected hematopoetic stem cells to engraft/recover will be compared with historical COBE Spectra engraftment/recovery data.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days Until Neutrophil Recovery Following Peripheral Blood Stem Cell Transplant Minus the Historical Median Day Until Recovery. | Neutrophil recovery is defined as the day on which the peripheral blood absolute neutrophil count exceeds 500/μL (ANC500)for the first of three consecutive measurements obtained on different days following transplant of peripheral blood stem cells in patients treated with myeloablative therapy for their underlying disease. As this was a test of non-inferiority, the null hypothesis to be tested (H0) was that the difference between the observed day to neutrophil recovery and the historical median day of neutrophil recovery was greater than two days. At two of the enrolling sites, Duke and Emory Universities, the median day to ANC500 was 12, while at the other two sites, Indiana University and the University of Utah, it was 11 days. Consequently, in the equation below, site specific-historic medians were compared to the observed days to achieve ANC500. H0: D > |2|, where D = Observed median day of neutrophil recovery - Site specific historic median day of neutrophil recovery. | up to 28 days following transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days Until Platelet Recovery | The time to platelet recovery is defined as the day following stem-cell transplant (Day 0) on which the platelet count exceeds 20,000/μL, for the first of three consecutive measurements obtained on different days, without platelet transfusion support within the preceding 7 days. | up to 28 days following transplant | 
| CD34+ Cell Collection Efficiency. | Collection efficiency (CE) is defined as the percentage of any given cellular subset, processed by the system, that is collected from the subject. CD34+ is a cell surface marker found on pluripotent hematopoeitic stem cells. | up to 7 days | 
| Mononuclear Cel (MNC) Collection Efficiency | Collection efficiency (CE) is defined as the percentage of any given cellular subset, processed by the system, that is collected from the subject. Determination of collection efficiency depends on an estimate of the average concentration of target cells in the patient's blood. Because these cells are continuously being removed during the collection, and are undergoing variable replacement from the bone marrow, this estimate will not be completely accurate. Underestimation of the concentration of target cells processed can lead to collection efficiencies of greater than 100%. | up to 7 days | 
| Platelet Collection Efficiency | Platelet contamination of the cell product was measured as the platelet collection efficiency, that is, as the percent of platelets processed that were collected. | up to 7 days | 
| Hematocrit of MNC Product | The hematocrit of the collected product was used to quantitate Red Blood Cell (RBC) contamination. | 7 days | 
| Granulocyte % of MNC Product | Granulocyte contamination of the MNC product was quantitated as the percent of total product White Blood Cells (WBC) that were segmented granulocytes or bands. | 7 days |