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| ID | Type | Description | Link |
|---|---|---|---|
| 12-C-0074 |
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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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hematopoietic Progenitor Cells (HPC) | Experimental | Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent use in various clinical protocols. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Filgrastim | Drug | Filgrastim will be administered as a single daily dose in a dose range of 10-16ug/kg/day subcutaneously for 5-7days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 of 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 | Progenitor cells by apheresis was determined by flow cytometry. | Through Day 2 of collection |
| 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. | Through Day 2 of collection |
| 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. | Through Day 2 of collection |
| Range of Cluster of Differentiation 34 (CD34) Cells Collected | Progenitor cells by apheresis was determined by flow cytometry. | Through Day 2 of collection |
| 25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected | Progenitor cells by apheresis was determined by flow cytometry. | Through Day 2 of collection |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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).
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.
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Kanakry, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18287387 | Background | Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20. | |
| 2301376 | Background | Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 10^6 CD34+ cells/kg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | percentage of patients | Day 1 of apheresis |
|
27 months and 27 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hematopoietic Progenitor Cells | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
The sample size in outcome measure number 6 was inadequate. Results were not conclusive and the information is determined to be too preliminary to present. No conclusion should be drawn from the reported data for this outcome.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Kanakry | National Cancer Institute | 301-451-3787 | kanakryja@nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Sep 23, 2017 | Dec 27, 2017 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| C088327 | plerixafor |
| D001781 | Blood Component Removal |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
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|
| Plerixafor | Drug | Plerixafor will be given on day 4, 8-10 hours before the day 5 apheresis, dose calculated according to patient weight |
|
|
| Apheresis | Procedure | 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. |
|
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. |
| Indefinitely until a referring physician requests the product for standard clinical care or until product(s) is no longer needed and disposed of |
| 27 months and 27 days |
| 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 | One week of mobilization therapy |
| 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. | Through Day 2 of collection |
| 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. | Day one of collection |
| Degree of Tumor Cell Contamination in the Final Product | Flow cytometry to detect tumor contamination. | Day 1 of apheresis |
| Impact of Plerixafor in the Degree of Tumor Cell Contamination in the Final Product | Flow cytometry to detect tumor contamination. | Day 1 of apheresis |
| 15693790 | Background | Tosi P, Zamagni E, Cellini C, Plasmati R, Cangini D, Tacchetti P, Perrone G, Pastorelli F, Tura S, Baccarani M, Cavo M. Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol. 2005 Mar;74(3):212-6. doi: 10.1111/j.1600-0609.2004.00382.x. |
| 27735212 | Background | Ogunniyi A, Rodriguez M, Devlin S, Adel N, Landau H, Chung DJ, Lendvai N, Lesokhin A, Koehne G, Mailankody S, Korde N, Reich L, Landgren O, Giralt S, Hassoun H. Upfront use of plerixafor and granulocyte-colony stimulating factor (GCSF) for stem cell mobilization in patients with multiple myeloma: efficacy and analysis of risk factors associated with poor stem cell collection efficiency. Leuk Lymphoma. 2017 May;58(5):1123-1129. doi: 10.1080/10428194.2016.1239261. Epub 2016 Oct 13. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| 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. | Posted | Number | percentage of patients | Through Day 2 of collection |
|
|
|
| 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. | Posted | Mean | Standard Deviation | Number of CD34 cells per kg/BW (x 10EE6) | Through Day 2 of collection |
|
|
|
| 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. | Posted | Median | Standard Deviation | Number of CD34 cells per kg/BW (x 10EE6) | Through Day 2 of collection |
|
|
|
| Primary | Range of Cluster of Differentiation 34 (CD34) Cells Collected | Progenitor cells by apheresis was determined by flow cytometry. | Posted | Median | Full Range | Number of CD34 cells per kg/BW (x 10EE6) | Through Day 2 of collection |
|
|
|
| Primary | 25th and 75th Percentile Values of Cluster of Differentiation 34 (CD34) Cells Collected | Progenitor cells by apheresis was determined by flow cytometry. | Posted | Number | Number of CD34 cells per kg/BW (x 10EE6) | Through Day 2 of collection |
|
|
|
| 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. | Posted | Number | products | Indefinitely until a referring physician requests the product for standard clinical care or until product(s) is no longer needed and disposed of |
|
|
|
| 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. | Posted | Count of Participants | Participants | 27 months and 27 days |
|
|
|
| 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 | Posted | Number | percentage of patients | One week of mobilization therapy |
|
|
|
| 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. | Posted | Number | percentage of patients | Through Day 2 of collection |
|
|
|
| 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. | Posted | Number | percentage of patients | Day one of collection |
|
|
|
| Secondary | Degree of Tumor Cell Contamination in the Final Product | Flow cytometry to detect tumor contamination. | No data from any participant was sufficiently collected to assess tumor cell contamination. | Posted | Day 1 of apheresis |
|
|
| Secondary | Impact of Plerixafor in the Degree of Tumor Cell Contamination in the Final Product | Flow cytometry to detect tumor contamination. | 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. | Posted | Day 1 of apheresis |
|
|
| 0 |
| 49 |
| 0 |
| 49 |
| 16 |
| 49 |
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Phlebitis | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D013812 | Therapeutics |