Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Stem cell mobilization, apheresis
Brief summary
This study will examine whether 240 µg/kg plerixafor given alone for up to 4 days is safe and well tolerated in multiple myeloma (MM) patients. In addition, this study determines if plerixafor alone can be used to mobilize peripheral blood progenitor cells (PBPCs) for transplantation in MM patients. The minimum number of CD34+ cells to collect is 2\*10\^6 CD34+ cells/kg and the target is ≧4\*10\^6 CD34+ cells/kg. Success of transplant engraftment will be measured by the number of days to polymorphonuclear leukocytes (PMN) and platelet (PLT) engraftment. Durability of transplant will be assessed for a minimum of one year.
Detailed description
This study will examine whether 240 µg/kg plerixafor given alone for up to 4 days is safe and well tolerated in multiple myeloma (MM) patients. In addition, this study determines if 240 µg/kg plerixafor alone can be used to mobilize peripheral blood progenitor cells (PBPCs) for transplantation in MM patients. The minimum number of CD34+ cells to collect is 2\*10\^6 CD34+ cells/kg and the target is ≧4\*10\^6 CD34+ cells/kg. Success of transplant engraftment will be measured by the number of days to polymorphonuclear leukocytes (PMN) and platelet (PLT) engraftment. Durability of engraftment will be assessed for a minimum of one year. This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.
Interventions
DRUGplerixafor
Participants were given a 240 µg/kg dose of plerixafor by subcutaneous injection in the morning followed by apheresis 6 hours later. Daily treatment with plerixafor followed by apheresis was administered for up to 4 consecutive days or until 4\*10\^6 CD34+ cells/kg body weight had been collected.
Sponsors
AnorMED
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of multiple myeloma (MM) * Eligible for autologous transplantation * Patients in first or second partial remission (PR) or complete remission (CR) * Patients who have received ≦2000 rads of prior radiation therapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Recovered from all acute toxic effects of prior chemotherapy * White blood cells (WBC) \>3.0\*10\^9/l * Absolute polymorphonuclear leucocyte (PMN) count \>1.5\*10\^9/l * Platelet (PLT) count \> 150\*10\^9/l * Serum creatinine ≦2.2 mg/dl * Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin \<2 x upper limit of normal (ULN) * Negative for HIV * Signed informed consent * Patients of childbearing potential agree to use an approved form of contraception
Exclusion criteria
* Patient received 2 or more alkylating agents, such as VBMCP (a combination of Vincristine, BCNU (Bis-Chloronitrosourea), Melphalan, Cyclophosphamide, and Prednisone) * Patient received a total dose of ≧200 mg of prior melphalan * A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications * Patient has failed previous collections or collection attempts * A residual acute medical condition resulting from prior chemotherapy * Brain metastases or carcinomatous meningitis * Acute infection * Fever (temperature \>38 °C / 100.4 °F) * Hypercalcemia (\>1mg/dl above ULN) * Positive pregnancy test in female patients * Lactating females * Patients of childbearing potential unwilling to implement adequate birth control * Patients whose actual body weight exceeds 175% of their ideal body weight * History of ventricular arrhythmias * Patient received thalidomide within 10 days prior to receiving the first dose of plerixafor * Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol or who are currently enrolled in another experimental protocol during the mobilization phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved ≥4*10^6 CD34+ Cells/kg | Day 1 up to day 4 | Number of participants achieving a target of ≥ 4\*10\^6 CD34+ cells/kg during apheresis for up to 4 consecutive days. Apheresis was performed six hours following treatment with plerixafor 240 µg/kg (alone). Target was calculated as the sum of all daily values collected from central laboratory data over up to 4 apheresis days. |
| Participant Counts of Summarized Adverse Events (AE) During Treatment | 1 month | Participant counts of summarized adverse events (AEs) which occurred from the first dose of plerixafor up to the day prior to chemotherapy/ablative treatment. Events were graded according to World Health Organization criteria: Mild (awareness of sign or symptom, but easily tolerated), Moderate (discomfort enough to cause interference with usual activity), Severe (incapacitating with inability to work or do usual activity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Transplantations That Achieved Polymorphonuclear Leukocyte (PMN) Engraftment Grouped by Days to Engraftment | Approximately 2 months | Polymorphonuclear cell (PMN) engraftment was defined as a PMN count ≥ 0.5\*10\^9/L for 3 consecutive days or ≥ 1\*10\^9/L for 1 day. Days to engraftment corresponded to the first day that the criteria were met after transplantation. |
| Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment | Approximately 2 months | Platelet (PLT) engraftment was defined as a PLT count of ≥ 20\*10\^9/L for 7 days without transfusion. Days to engraftment corresponded to the first day that the criteria were met after transplantation. |
| Number of Participants With a Durable Graft at 12 Months Post Transplantation | Approximately month 13 | Graft durability was assessed by the Investigator based on complete blood count (CBC) and differential analyses at 12 months post transplantation. |
Countries
United States
Participant flow
Recruitment details
Study enrollment began in November 2004 and the study was terminated in May 2007. A total of 20 participants were planned for this study, however the study was terminated early because of insufficient mobilization of CD34+ cells after treatment with plerixafor alone for use in tandem transplants.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Multiple Myeloma (MM) Participants with MM who were eligible for autologous peripheral blood stem cell transplantation were given 240 µg/kg daily subcutaneous plerixafor for up to 4 days. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Participants With Multiple Myeloma (MM) |
|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Number of Participants Who Achieved ≥4*10^6 CD34+ Cells/kg
Number of participants achieving a target of ≥ 4\*10\^6 CD34+ cells/kg during apheresis for up to 4 consecutive days. Apheresis was performed six hours following treatment with plerixafor 240 µg/kg (alone). Target was calculated as the sum of all daily values collected from central laboratory data over up to 4 apheresis days.
Time frame: Day 1 up to day 4
Population: All participants who received plerixafor
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Multiple Myeloma (MM) | Number of Participants Who Achieved ≥4*10^6 CD34+ Cells/kg | Participants Who Achieved ≥4*10^6 cells | 4 participants |
| Participants With Multiple Myeloma (MM) | Number of Participants Who Achieved ≥4*10^6 CD34+ Cells/kg | Participants Who Achieved <4*10^6 cells | 5 participants |
Primary
Participant Counts of Summarized Adverse Events (AE) During Treatment
Participant counts of summarized adverse events (AEs) which occurred from the first dose of plerixafor up to the day prior to chemotherapy/ablative treatment. Events were graded according to World Health Organization criteria: Mild (awareness of sign or symptom, but easily tolerated), Moderate (discomfort enough to cause interference with usual activity), Severe (incapacitating with inability to work or do usual activity).
Time frame: 1 month
Population: All participants who received plerixafor
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Severity (Mild) | 3 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Severity (Moderate) | 6 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Severity (Severe) | 0 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | Life-threatening AE | 0 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Relationship to Drug (Not related) | 4 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Relationship to Drug (Probably not related) | 1 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Relationship to Drug (Possibly related) | 1 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Relationship to Drug (Probably related) | 3 participants |
| Participants With Multiple Myeloma (MM) | Participant Counts of Summarized Adverse Events (AE) During Treatment | AE Relationship to Drug (Definitely related) | 0 participants |
Secondary
Number of Participants With a Durable Graft at 12 Months Post Transplantation
Graft durability was assessed by the Investigator based on complete blood count (CBC) and differential analyses at 12 months post transplantation.
Time frame: Approximately month 13
Population: Intent to treat population includes participants who received plerixafor, underwent transplantation, and were evaluable 12 months post transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Multiple Myeloma (MM) | Number of Participants With a Durable Graft at 12 Months Post Transplantation | 6 participants |
Secondary
Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment
Platelet (PLT) engraftment was defined as a PLT count of ≥ 20\*10\^9/L for 7 days without transfusion. Days to engraftment corresponded to the first day that the criteria were met after transplantation.
Time frame: Approximately 2 months
Population: Intent to treat population includes participants who received plerixafor and underwent transplantation. One participant had two transplants. One participant did not have PLT samples collected (included as 'unknown' in data table).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment | <= Day 12 post transplant | 0 transplantations |
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment | Day 13 to 21 post transplant | 6 transplantations |
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment | >= Day 22 post transplant | 3 transplantations |
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Platelet (PLT) Engraftment Grouped by Days to Engraftment | Unknown | 1 transplantations |
Secondary
Number of Transplantations That Achieved Polymorphonuclear Leukocyte (PMN) Engraftment Grouped by Days to Engraftment
Polymorphonuclear cell (PMN) engraftment was defined as a PMN count ≥ 0.5\*10\^9/L for 3 consecutive days or ≥ 1\*10\^9/L for 1 day. Days to engraftment corresponded to the first day that the criteria were met after transplantation.
Time frame: Approximately 2 months
Population: Intent to treat population includes participants who received plerixafor and underwent transplantation. One participant had two transplants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Polymorphonuclear Leukocyte (PMN) Engraftment Grouped by Days to Engraftment | <= Day 12 post transplant | 10 transplantations |
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Polymorphonuclear Leukocyte (PMN) Engraftment Grouped by Days to Engraftment | Day 13 to 21 post transplant | 0 transplantations |
| Participants With Multiple Myeloma (MM) | Number of Transplantations That Achieved Polymorphonuclear Leukocyte (PMN) Engraftment Grouped by Days to Engraftment | >= Day 22 post transplant | 0 transplantations |
Post Hoc
Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg
Number of participants achieving ≥ 2\*10\^6 CD34+ cells/kg during apheresis for up to 4 consecutive days. Apheresis was performed six hours following treatment with plerixafor 240 µg/kg (alone). Total was calculated as the sum of all daily values collected from central laboratory data over up to 4 apheresis days.
Time frame: Day 1 up to day 4
Population: All participants who received plerixafor
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Multiple Myeloma (MM) | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg | 9 participants |