Multiple Myeloma, Plasma Cell Myeloma
Conditions
Keywords
Autologous Hematopoietic Cell Transplantation, Plasma Cell Myeloma, Mobilization, Apheresis, Plerixafor
Brief summary
Background: \- One beneficial treatment for plasma cell myeloma is high-dose chemotherapy followed by stem cell transplant. Researchers want to collect stem cells from the blood for later transplant. Objectives: \- To collect stem cells for transplant as part of treatment for plasma cell myeloma. Eligibility: \- Individuals at least 18 years of age who will have chemotherapy and stem cell transplant for plasma cell myeloma. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Participants will have filgrastim injections for 5 days before collection. This will move stem cells from the bone marrow to the blood. * Participants will have apheresis to collect the stem cells. * Participants who need additional apheresis procedures to collect stem cells will have filgrastim and a dose of plerixafor to improve the collection yield.
Detailed description
Background: High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) remains a critical part of the Plasma Cell Myeloma (PCM) treatment in subjects eligible for the procedure. The timing of the procedure however, has become more controversial recently. This protocol will allow collection of Hematopoietic Progenitor Cells by Apheresis (HPC, Apheresis) in potential candidates for various PCM protocols at the Clinical Center. The mobilizing agent plerixafor (Mozobil, Genzyme) has been recently approved by the Food and Drug Administration (FDA) for mobilization in PCM. However, the best and most cost effective strategy for its use remains to be defined. Objectives: Evaluate the overall validity of an HPC mobilization strategy (with granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor) using a formula calculating the likelihood of collecting greater than or equal to 5 time 10\^6 cluster of differentiation 34 (CD34) plus cells/kg in a single mobilization cycle. Collect mobilized Hematopoietic Progenitor Cells by Apheresis (HPC, Apheresis) prior to AHCT for PCM Eligibility: Subjects with a possible indication for AHCT for the treatment of newly diagnosed PCM. Subjects with recurrent or persistent evaluable disease who have not undergone AHCT for the treatment of the PCM. Design: Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent use in various clinical protocols. Mobilization will be provided by a 5-daily administration of filgrastim according to standard procedure. The need for an additional mobilizing agent (plerixafor) to be given on day 4 of mobilization will be evaluated in real time in each patient, based on the peripheral blood CD34 count on the morning of day 4 of filgrastim administration. Study accrual over a 3-year period: 70 subjects
Interventions
DRUGFilgrastim
Filgrastim will be administered as a single daily dose in a dose range of 10-16ug/kg/day subcutaneously for 5-7days
DRUGPlerixafor
Plerixafor will be given on day 4, 8-10 hours before the day 5 apheresis, dose calculated according to patient weight
PROCEDUREApheresis
The minimum cluster of differentiation 34 (CD34)+ cell dose that must be collected in order to proceed with a single autologous transplantation is 2 x 106 CD34+ cells/kg.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Multiple Myeloma Criteria: Subjects with an indication for autologous hematopoietic cell transplant (AHCT) for the treatment of PCM as determined by the principal investigator (PI) or lead associate investigator (LAI). * Subjects following induction treatment for plasma cell myeloma (PCM) * Subjects with recurrent or persistent evaluable disease who have not undergone AHCT for the treatment of the PCM. Other Eligibility Criteria: Age greater than or equal to 18 years and less than or equal to 75 years. In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling. Karnofsky performance status of 70% or greater (Eastern Cooperative Oncology Group ((ECOG) 0 or 1) Ejection fraction (EF) by multigated acquisition scan (MUGA) or 2-D echocardiogram within institution normal limits. In case of low ejection fraction (EF), the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more. Hemoglobin (Hgb) greater than or equal to 8 g/dl (transfusion acceptable) No history of abnormal bleeding tendency. Patients must be able to give informed consent
Exclusion criteria
Prior allogeneic stem cell transplantation Hypertension not adequately controlled by 3 or less medications. Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting this exclusion criterion will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis. Should the cardiologist deem the patients findings on work-up to be not clinically significant pathology, the patient will have met this exclusion criterion. Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis. Active hepatitis B or C infection Human immunodeficiency virus (HIV) seropositive, with positive confirmatory nucleic acid test Patients known or found to be pregnant. Patients of childbearing age who are unwilling to practice contraception. Patients may be excluded at the discretion of the principal investigator (PI)/lead associate investigator (LAI) if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Hematopoietic Progenitor Cell (HPC) Apheresis Products Collected and Cryopreserved for Subsequent Use in Autologous Hematopoietic Cell Transplantation (AHCT) in Subjects With Plasma Cell Myeloma (PCM) | Indefinitely until a referring physician requests the product for standard clinical care or until product(s) is no longer needed and disposed of | The cryopreserved stem cells are stored under Good Manufacturing Practice (GMP) conditions in the National Institutes of Health (NIH) Department of Transfusion Medicine until a referring physician requests the products for standard clinical care. |
| Percentage of Patients Achieving at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight on Day 1 of Apheresis | Day 1 of apheresis | Progenitor cells by apheresis was determined by flow cytometry. The stated goal was a minimum dose of 2x10EE\^6/kg following apheresis. |
| Percentage of Patients Requiring 2 Days to Achieve at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight | Through Day 2 of collection | Progenitor cells by apheresis was determined by flow cytometry. |
| Average Number of Cluster of Differentiation 34 (CD34) Cells Collected (Per kg Recipient Body Weight (BW)) | Through Day 2 of collection | Progenitor cells by apheresis was determined by flow cytometry. |
| Median and Standard Deviation of Cluster of Differentiation 34 (CD34) Cells Collected (Per Kg Recipient Body Weight) (BW) | Through Day 2 of collection | Progenitor cells by apheresis was determined by flow cytometry. |
| Range of Cluster of Differentiation 34 (CD34) Cells Collected | Through Day 2 of collection | Progenitor cells by apheresis was determined by flow cytometry. |
| 25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected | Through Day 2 of collection | Progenitor cells by apheresis was determined by flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients That Required Plerixafor + Granulocyte-colony Stimulating Factor (G-CSF) And Only G-CSF (no Plerixafor) | One week of mobilization therapy | Percentage of patients that required Plerixafor injection in addition to G-CSF mobilization or none at all |
| Percentage of Patients That Achieved or Did Not Achieve 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg | Through Day 2 of collection | Here is the percentage of patients that achieved or did not achieve 5 x 10\^6 CD34 cells/kg in a single apheresis. |
| Percentage of Patients That Achieved ≥ 2 x 10^6 But Less Than 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg (Day One Collection) | Day one of collection | Percentage of patents achieving collecting the minimum but not optimal CD34 cell number. |
| Degree of Tumor Cell Contamination in the Final Product | Day 1 of apheresis | Flow cytometry to detect tumor contamination. |
| Impact of Plerixafor in the Degree of Tumor Cell Contamination in the Final Product | Day 1 of apheresis | Flow cytometry to detect tumor contamination. |
| Number of Participants With Serious and Non-Serious Adverse Events | 27 months and 27 days | Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Participant flow
Pre-assignment details
Our study was a relatively small pilot study, with the primary emphasis being on expanding standard stem cell therapy options for patients with multiple myeloma. The plerixafor plus G-CSF combination is used relatively ubiquitously, and several larger studies relating to plerixafor have been performed at large centers that treat multiple myeloma.
Participants by arm
| Arm | Count |
|---|---|
| Hematopoietic Progenitor Cells (HPC) Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent use in various clinical protocols.
Filgrastim: Filgrastim will be administered as a single daily dose in a dose range of 10-16ug/kg/day subcutaneously for 5-7days
Plerixafor: Plerixafor will be given on day 4, 8-10 hours before the day 5 apheresis, dose calculated according to patient weight
Apheresis: The minimum cluster of differentiation 34 (CD34)+ cell dose that must be collected in order to proceed with a single autologous transplantation is 2 x 106\^ CD34+ cells/kg. | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Hematopoietic Progenitor Cells (HPC) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age, Continuous | 56.99 years STANDARD_DEVIATION 8.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 49 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 49 |
| other Total, other adverse events | 16 / 49 |
| serious Total, serious adverse events | 0 / 49 |
Outcome results
Primary
25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected
Progenitor cells by apheresis was determined by flow cytometry.
Time frame: Through Day 2 of collection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | 25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected | 25th percentile | 4.0 Number of CD34 cells per kg/BW (x 10EE6) |
| Hematopoietic Progenitor Cells (HPC) | 25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected | 75th percentile | 8.0 Number of CD34 cells per kg/BW (x 10EE6) |
Primary
Average Number of Cluster of Differentiation 34 (CD34) Cells Collected (Per kg Recipient Body Weight (BW))
Progenitor cells by apheresis was determined by flow cytometry.
Time frame: Through Day 2 of collection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Average Number of Cluster of Differentiation 34 (CD34) Cells Collected (Per kg Recipient Body Weight (BW)) | 6.4 Number of CD34 cells per kg/BW (x 10EE6) | Standard Deviation 2.8 |
Primary
Median and Standard Deviation of Cluster of Differentiation 34 (CD34) Cells Collected (Per Kg Recipient Body Weight) (BW)
Progenitor cells by apheresis was determined by flow cytometry.
Time frame: Through Day 2 of collection
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Median and Standard Deviation of Cluster of Differentiation 34 (CD34) Cells Collected (Per Kg Recipient Body Weight) (BW) | 6.3 Number of CD34 cells per kg/BW (x 10EE6) | Standard Deviation 2.8 |
Primary
Number of Hematopoietic Progenitor Cell (HPC) Apheresis Products Collected and Cryopreserved for Subsequent Use in Autologous Hematopoietic Cell Transplantation (AHCT) in Subjects With Plasma Cell Myeloma (PCM)
The cryopreserved stem cells are stored under Good Manufacturing Practice (GMP) conditions in the National Institutes of Health (NIH) Department of Transfusion Medicine until a referring physician requests the products for standard clinical care.
Time frame: Indefinitely until a referring physician requests the product for standard clinical care or until product(s) is no longer needed and disposed of
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Number of Hematopoietic Progenitor Cell (HPC) Apheresis Products Collected and Cryopreserved for Subsequent Use in Autologous Hematopoietic Cell Transplantation (AHCT) in Subjects With Plasma Cell Myeloma (PCM) | 49 products |
Primary
Percentage of Patients Achieving at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight on Day 1 of Apheresis
Progenitor cells by apheresis was determined by flow cytometry. The stated goal was a minimum dose of 2x10EE\^6/kg following apheresis.
Time frame: Day 1 of apheresis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients Achieving at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight on Day 1 of Apheresis | 98 percentage of patients |
Primary
Percentage of Patients Requiring 2 Days to Achieve at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight
Progenitor cells by apheresis was determined by flow cytometry.
Time frame: Through Day 2 of collection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients Requiring 2 Days to Achieve at Least 2 x 10^6 Cluster of Differentiation 34 (CD34) Cells Per Kg Recipient Body Weight | 2 percentage of patients |
Primary
Range of Cluster of Differentiation 34 (CD34) Cells Collected
Progenitor cells by apheresis was determined by flow cytometry.
Time frame: Through Day 2 of collection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Range of Cluster of Differentiation 34 (CD34) Cells Collected | 6.3 Number of CD34 cells per kg/BW (x 10EE6) |
Secondary
Degree of Tumor Cell Contamination in the Final Product
Flow cytometry to detect tumor contamination.
Time frame: Day 1 of apheresis
Population: No data from any participant was sufficiently collected to assess tumor cell contamination.
Secondary
Impact of Plerixafor in the Degree of Tumor Cell Contamination in the Final Product
Flow cytometry to detect tumor contamination.
Time frame: Day 1 of apheresis
Population: Because no data from any participant was sufficiently collected to assess tumor cell contamination, we were not able to determine the effect of plerixafor on this parameter.
Secondary
Number of Participants With Serious and Non-Serious Adverse Events
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: 27 months and 27 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Number of Participants With Serious and Non-Serious Adverse Events | 16 Participants |
Secondary
Percentage of Patients That Achieved ≥ 2 x 10^6 But Less Than 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg (Day One Collection)
Percentage of patents achieving collecting the minimum but not optimal CD34 cell number.
Time frame: Day one of collection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients That Achieved ≥ 2 x 10^6 But Less Than 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg (Day One Collection) | 31 percentage of patients |
Secondary
Percentage of Patients That Achieved or Did Not Achieve 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg
Here is the percentage of patients that achieved or did not achieve 5 x 10\^6 CD34 cells/kg in a single apheresis.
Time frame: Through Day 2 of collection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients That Achieved or Did Not Achieve 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg | Achieved 5 x 10EE CD34 cells/kg | 65 percentage of patients |
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients That Achieved or Did Not Achieve 5 x 10^6 Cluster of Differentiation 34 (CD34) Cells/kg | Did not achieve 5 x 10EE CD34 cells/kg | 35 percentage of patients |
Secondary
Percentage of Patients That Required Plerixafor + Granulocyte-colony Stimulating Factor (G-CSF) And Only G-CSF (no Plerixafor)
Percentage of patients that required Plerixafor injection in addition to G-CSF mobilization or none at all
Time frame: One week of mobilization therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients That Required Plerixafor + Granulocyte-colony Stimulating Factor (G-CSF) And Only G-CSF (no Plerixafor) | Plerixafor + G-CSF | 47 percentage of patients |
| Hematopoietic Progenitor Cells (HPC) | Percentage of Patients That Required Plerixafor + Granulocyte-colony Stimulating Factor (G-CSF) And Only G-CSF (no Plerixafor) | Only G-CSF (no plerixafor) | 53 percentage of patients |