Multiple Myeloma
Conditions
Brief summary
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
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.
Interventions
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.
Sponsors
Terumo BCT
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days Until Neutrophil Recovery Following Peripheral Blood Stem Cell Transplant Minus the Historical Median Day Until Recovery. | up to 28 days following transplant | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD34+ Cell Collection Efficiency. | up to 7 days | 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. |
| Mononuclear Cel (MNC) Collection Efficiency | up to 7 days | 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%. |
| Days Until Platelet Recovery | up to 28 days following transplant | 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. |
| Hematocrit of MNC Product | 7 days | The hematocrit of the collected product was used to quantitate Red Blood Cell (RBC) contamination. |
| Granulocyte % of MNC Product | 7 days | Granulocyte contamination of the MNC product was quantitated as the percent of total product White Blood Cells (WBC) that were segmented granulocytes or bands. |
| Platelet Collection Efficiency | up to 7 days | Platelet contamination of the cell product was measured as the platelet collection efficiency, that is, as the percent of platelets processed that were collected. |
Countries
United States
Participant flow
Recruitment details
Patients requiring a first peripheral blood stem cell collection and transplant for multiple myeloma were recruited at four clinical centers from March through October, 2011.
Pre-assignment details
This was a single arm study, which evaluated Multiple Myeloma patients who received autologous stem-cell transplants collected using the Spectra Optia Apheresis System, following myeloablative therapy. The study was limited to subjects who were expected to demonstrate normal neutrophil recovery.
Participants by arm
| Arm | Count |
|---|---|
| Patients With Multiple Myeloma Multiple myeloma patients requiring myeloablative therapy and a first autologous hematopoetic stem cell transplant. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Did not meet screening criteria | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Patients With Multiple Myeloma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age Continuous | 63 years |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
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.
Time frame: up to 28 days following transplant
Population: Twenty-six patients were evaluable per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Days Until Neutrophil Recovery Following Peripheral Blood Stem Cell Transplant Minus the Historical Median Day Until Recovery. | 0 Days |
Comparison: The null hypothesis was that the median day to neutrophil recovery in this study was more than two days longer than historical controls.p-value: <0.02595% CI: [0, 0]Hodges-Lehman estimation
Secondary
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.
Time frame: up to 7 days
Population: Data to calculate CD34+ cell collection efficiency was available for 39 collections on 24 of 26 per protocol patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | CD34+ Cell Collection Efficiency. | 70 % of processed CD34+ cells collected |
Secondary
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.
Time frame: up to 28 days following transplant
Population: All per protocol patients for whom platelet recovery data was available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Days Until Platelet Recovery | 20 days |
Secondary
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.
Time frame: 7 days
Population: Data to calculate the percent of product WBCs that were segmented granulocytes or bands was available for 38 MNC collections on 25 of the 26 per protocol patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Granulocyte % of MNC Product | 29.0 percentage of product WBCs |
Secondary
Hematocrit of MNC Product
The hematocrit of the collected product was used to quantitate Red Blood Cell (RBC) contamination.
Time frame: 7 days
Population: Data was available from 38 MNC collections from 25 of the 26 per protocol patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Hematocrit of MNC Product | 1.8 hematocrit % |
Secondary
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%.
Time frame: up to 7 days
Population: Data was available to calculate MNC collection efficiency on 35 collections performed on 22 of the 26 per protocol patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Mononuclear Cel (MNC) Collection Efficiency | 60 % of processed MNCs that were collected |
Secondary
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.
Time frame: up to 7 days
Population: Data to calculate platelet collection efficiency was available for 38 MNC collections on 24 of the 26 per protocol patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Multiple Myeloma | Platelet Collection Efficiency | 19 % of processed platelets collected |