Autologous Stem Cell Transplantation
Conditions
Keywords
Multiple Myeloma, Non-Hodgkin's Lymphoma, autologous transplantation, AMD3100, stem cell mobilization, plerixafor
Brief summary
This study evaluates the safety, efficacy, and pharmacokinetics (PK) of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients who would benefit from an autologous stem cell transplant but have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 (plerixafor) on the evening prior to each day of apheresis. Efficacy outcomes include quantification of CD34+ cells in the apheresis product and assessment of successful polymorphonuclear leukocyte (PMN) and platelet (PLT) engraftment after transplantation. PK outcomes include analysis of repeated doses of plerixafor.
Detailed description
This is a Phase 2, multicenter, prospective, open-label study. Once 70 patients have enrolled, subsequent patients enrolled should have a diagnosis of lymphoma. Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF) alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests, and who meet the inclusion/exclusion criteria are eligible to receive plerixafor as outlined in this protocol. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of plerixafor on the evening prior to each day of apheresis. Patients will undergo mobilization with G-CSF (10 µg/kg) for 4 days. On Day 4, plerixafor (240 µg/kg) will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter, such that there is a 10 to 11 hour interval between dosing and the initiation of apheresis. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≥2\*10\^6 CD34+ cells/kg are collected, whichever occurs first. In addition, the mobilization of NHL tumor cells and the pharmacokinetics of repeat doses of plerixafor will be examined. After the last apheresis has been completed, or after the patient has collected ≥2\*10\^6 CD34+ cells/kg, he/she will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with plerixafor mobilization regimen. In the event that the minimum number of ≥2\*10\^6 cells for transplantation are not obtained from the first mobilization with plerixafor, cells may be retained and pooled for transplantation with those from a second mobilization with plerixafor (or from prior mobilization with other agents), at the investigator's discretion. If a second mobilization with plerixafor is attempted, a minimum rest interval of one week should be allowed between the last apheresis of the first regimen and the first dose of G-CSF of the second. The number of CD34+ cells mobilized in the peripheral blood (PB), collected in the apheresis product, and the number of apheresis sessions performed will be measured. Success of the transplantation will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN) and platelets (PLT). Participants will be assessed for durability of their transplant for 12 months after transplantation. 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
Participants underwent mobilization with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection each morning. On the evening of Day 4, participants received a dose of plerixafor 240 µg/kg, administered by SC injection. On Day 5, participants returned to the clinic and received a morning dose of G-CSF 10 µg/kg and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor (within 60 minutes after administration of G-CSF). Participants continued to receive an evening dose of plerixafor followed the next day by a morning dose of G-CSF and apheresis for up to a maximum of 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected.
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Eligible to undergo autologous transplantation * Has failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF), chemotherapy and G-CSF or any other conventional therapy including cytokines, chemotherapy and cytokines or bone marrow harvest. * Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 * ≥3 weeks since last cycle of chemotherapy (thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study) NOTE: Although thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study, none are to be administered within 7 days prior to the first dose of G-CSF (see
Exclusion criteria
). * The patient has recovered from all acute toxic effects of prior chemotherapy * White blood cell count (WBC) \>2.5\*10\^9/L * Absolute neutrophil count \>1.5\*10\^9/L * Platelet count \>85\*10\^9/L * Serum creatinine ≤1.5 mg/dl * Creatinine clearance \>60 ml/min * Aspartate aminotransferase (AST), alanine transaminase (ALT) and total bilirubin \<2x upper limit of normal (ULN) * Left ventricle ejection fraction \>45% (by normal echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan) * Forced expiratory volume in one minute (FEV1) \>60% of predicted or diffusion lung capacity for carbon monoxide (DLCO) ≥45% of predicted * No active infection of hepatitis B or C * Negative for HIV * Signed informed consent * Women of child-bearing potential agree to use an approved form of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Day 1 to approximately day 38 | Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related'). |
| Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Day 5 to Day 11 (up to 7 apheresis) | Proportion of participants who reached the target of at least 2\*10\^6 CD34+ cells/kg collected during up to 7 aphereses. |
| Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Day 5 to Day 11 (up to 7 aphereses) | Proportion of participants who reached the target of at least 5\*10\^6 CD34+ cells/kg collected during up to 7 apheresis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Non-Hodgkin's Lymphoma (NHL) Who Had Evidence of Tumor Cell Mobilization After G-CSF or Plerixafor Administration | Up to Day 7 | The number of participants with Bcl2 translocation in post-treatment samples. |
| Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | Day 5 up to Month 6 (up to 7 aphereses in each course of treatment) | Number of participants who had at least 2\*10\^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together. |
| Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | Day 5 up to Month 6 (up to 7 aphereses in each course of treatment) | Number of participants who had at least 5\*10\^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together. |
| Maximum Observed Plasma Concentration (Cmax) on Day 4 | Day 4 (following first plerixafor administration) | Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data. |
| Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | approximately 2 months (1 month post transplant) | The number of days from transplantation to successful engraftment as measured by PMN \>=0.5\*10\^9 /L for 3 days or \>=1.0\*10\^9 /L for 1 day. |
| Time to Maximum Plasma Concentration (Tmax) on Day 4 | Day 4 (following first plerixafor administration) | Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data |
| Time to Maximum Plasma Concentration (Tmax) on Day 7 | Day 7 (following fourth plerixafor administration) | Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data |
| Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 4 | Days 4 -5 (following first plerixafor administration) | Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule. |
| Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 7 | Days 7-8 (following fourth plerixafor administration) | Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule. |
| Maximum Observed Plasma Concentration (Cmax) on Day 7 | Day 7 (following fourth plerixafor administration) | Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data. |
| Median Number of Days to Platelet (PLT) Engraftment | Approximately 2 months (1 month post transplant) | The number of days from transplantation to successful engraftment as measured by platelet value of \>=20\*10\^9/L for 7 days without transfusion. |
| Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation | Approximately 13 months (12 months post transplant ) | The number of participants maintaining a durable graft 12 months after transplantation. A durable graft was defined as maintenance of normal blood counts: PLT \>50\*10\^9/L without transfusion for at least 2 weeks prior to the visit; hemoglobin level \>= 10 g/dL with no erythropoietin or transfusions for at least 1 month prior to the visit; and absolute neutrophil count (ANC) \> 1,000 (1\*10\^9/L) with no G-CSF for at least 1 week prior to the visit. |
Countries
United States
Participant flow
Pre-assignment details
Four participants were enrolled in the study but never received plerixafor treatment so are not included below. Reasons for not receiving plerixafor included disease progression (2), infection (1) and insurance issues (1).
Participants by arm
| Arm | Count |
|---|---|
| Non-Hodgkin's Lymphoma Participants with non-Hodgkin's lymphoma (NHL) were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected. | 66 |
| Hodgkin's Disease Participants with Hodgkin's disease (HD) were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected. | 21 |
| Multiple Myeloma Participants with multiple myeloma (MM) were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected. | 10 |
| Other Cancers Participants with 'other' cancers (desmoplastic small round cell tumor, acute myeloid leukemia, and testicular cancer) were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected. | 3 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 16 |
| Overall Study | Did not go on to transplant | 5 |
| Overall Study | Failed to mobilize - no transplant | 8 |
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Hodgkin's Disease | Multiple Myeloma | Non-Hodgkin's Lymphoma | Other Cancers | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 15.5 | 62.6 years STANDARD_DEVIATION 11.3 | 57.0 years STANDARD_DEVIATION 10 | 32.7 years STANDARD_DEVIATION 28.9 | 54.4 years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 2 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 1 participants | 3 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized Caucasian | 17 participants | 9 participants | 60 participants | 3 participants | 89 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 participants | 0 participants | 1 participants | 0 participants | 3 participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 29 Participants | 1 Participants | 45 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 37 Participants | 2 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 64 / 66 | 20 / 21 | 9 / 10 | 3 / 3 |
| serious Total, serious adverse events | 4 / 66 | 0 / 21 | 1 / 10 | 1 / 3 |
Outcome results
Primary
Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period
Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').
Time frame: Day 1 to approximately day 38
Population: Safety population of all participants who received at least 1 dose of plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Moderate | 18 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Definitely Related | 9 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Severe | 5 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Probably Related | 22 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Possibly Related | 16 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Mild | 42 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Participants Reporting At Least 1 AE | 65 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug-Probably Not Related | 8 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Not Related | 10 Participants |
| Non-Hodgkin's Lymphoma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Life Threatening | 0 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Mild | 12 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Participants Reporting At Least 1 AE | 20 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Moderate | 8 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Severe | 0 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Life Threatening | 0 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Not Related | 4 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug-Probably Not Related | 2 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Possibly Related | 4 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Probably Related | 2 Participants |
| Hodgkin's Disease | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Definitely Related | 8 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Not Related | 4 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Probably Related | 2 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Moderate | 1 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Severe | 1 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Mild | 7 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Life Threatening | 0 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug-Probably Not Related | 1 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Participants Reporting At Least 1 AE | 9 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Definitely Related | 1 Participants |
| Multiple Myeloma | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Possibly Related | 1 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Mild | 1 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Definitely Related | 2 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Participants Reporting At Least 1 AE | 3 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Moderate | 0 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Not Related | 0 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Possibly Related | 0 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Probably Related | 1 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug-Probably Not Related | 0 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Severe | 2 Participants |
| Other Cancers | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Life Threatening | 0 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Severe | 8 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Probably Related | 27 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Life Threatening | 0 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Not Related | 18 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Definitely Related | 20 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug-Probably Not Related | 11 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Participants Reporting At Least 1 AE | 97 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | AE Relationship to Study Drug -Possibly Related | 21 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Moderate | 27 Participants |
| All Patients | Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period | Adverse Events by Severity -Mild | 62 Participants |
Primary
Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
Proportion of participants who reached the target of at least 2\*10\^6 CD34+ cells/kg collected during up to 7 aphereses.
Time frame: Day 5 to Day 11 (up to 7 apheresis)
Population: Full analysis set of participants who received at least 1 dose of plerixafor. These results do not include results from the second course of plerixafor treatment and second course of apheresis for the 7 participants who had 2 courses of apheresis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | .773 Proportion of Participants |
| Hodgkin's Disease | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | .714 Proportion of Participants |
| Multiple Myeloma | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 1.00 Proportion of Participants |
| Other Cancers | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | .667 Proportion of Participants |
| All Patients | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | .780 Proportion of Participants |
Primary
Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
Proportion of participants who reached the target of at least 5\*10\^6 CD34+ cells/kg collected during up to 7 apheresis.
Time frame: Day 5 to Day 11 (up to 7 aphereses)
Population: Full analysis set of participants who received at least 1 dose of plerixafor. These results do not include results from the second course of plerixafor treatment and second course of apheresis for the 7 participants who had two courses of apheresis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 0.288 Proportion of Participants |
| Hodgkin's Disease | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 0.429 Proportion of Participants |
| Multiple Myeloma | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 0.70 Proportion of Participants |
| Other Cancers | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 0.667 Proportion of Participants |
| All Patients | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | 0.37 Proportion of Participants |
Secondary
Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 4
Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule.
Time frame: Days 4 -5 (following first plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Hodgkin's Lymphoma | Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 4 | 4578 ng*h/mL | Standard Deviation 1715 |
Secondary
Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 7
Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule.
Time frame: Days 7-8 (following fourth plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Hodgkin's Lymphoma | Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 7 | 5496 ng*h/mL | Standard Deviation 1339 |
Secondary
Maximum Observed Plasma Concentration (Cmax) on Day 4
Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data.
Time frame: Day 4 (following first plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Hodgkin's Lymphoma | Maximum Observed Plasma Concentration (Cmax) on Day 4 | 796 ng/mL | Standard Deviation 305 |
Secondary
Maximum Observed Plasma Concentration (Cmax) on Day 7
Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data.
Time frame: Day 7 (following fourth plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Hodgkin's Lymphoma | Maximum Observed Plasma Concentration (Cmax) on Day 7 | 894 ng/mL | Standard Deviation 227 |
Secondary
Median Number of Days to Platelet (PLT) Engraftment
The number of days from transplantation to successful engraftment as measured by platelet value of \>=20\*10\^9/L for 7 days without transfusion.
Time frame: Approximately 2 months (1 month post transplant)
Population: Participants who received a transplant and had a successful PLT engraftment. Seven participants (4 with HD, 2 with MM, and 1 with testicular cancer) received a second transplant. Four transplants (2 in participants with NHL and 2 in participants with MM) did not result in PLT engraftment and are therefore not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Median Number of Days to Platelet (PLT) Engraftment | 21.0 Days |
| Hodgkin's Disease | Median Number of Days to Platelet (PLT) Engraftment | 21.0 Days |
| Multiple Myeloma | Median Number of Days to Platelet (PLT) Engraftment | 19.0 Days |
| Other Cancers | Median Number of Days to Platelet (PLT) Engraftment | 26.0 Days |
| All Patients | Median Number of Days to Platelet (PLT) Engraftment | 21.0 Days |
Secondary
Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment
The number of days from transplantation to successful engraftment as measured by PMN \>=0.5\*10\^9 /L for 3 days or \>=1.0\*10\^9 /L for 1 day.
Time frame: approximately 2 months (1 month post transplant)
Population: Participants who received a transplant and had a successful PMN engraftment. Seven participants (4 with HD, 2 with MM, and 1 with testicular cancer) received a second transplant. Two transplants (1 in a participant with NHL and 1 in a participant with MM) did not result in PMN engraftment and are therefore not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 12.0 Days |
| Hodgkin's Disease | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 12.0 Days |
| Multiple Myeloma | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 13.0 Days |
| Other Cancers | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 10.0 Days |
| All Patients | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 12.0 Days |
Secondary
Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF
Number of participants who had at least 2\*10\^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together.
Time frame: Day 5 up to Month 6 (up to 7 aphereses in each course of treatment)
Population: Participants who received one course or two courses of plerixafor. Four NHL participants and 3 HD participants had two courses of plerixafor and the sum of CD34+ cells/kg collected in both courses is included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 54 Participants |
| Hodgkin's Disease | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 18 Participants |
| Multiple Myeloma | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 10 Participants |
| Other Cancers | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 2 Participants |
| All Patients | Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 84 Participants |
Secondary
Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF
Number of participants who had at least 5\*10\^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together.
Time frame: Day 5 up to Month 6 (up to 7 aphereses in each course of treatment)
Population: Participants who received one course or two courses of plerixafor. Four NHL participants and 3 HD participants had two courses of plerixafor and the sum of CD34+ cells/kg collected in both courses is included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 21 Participants |
| Hodgkin's Disease | Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 9 Participants |
| Multiple Myeloma | Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 7 Participants |
| Other Cancers | Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 2 Participants |
| All Patients | Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF | 39 Participants |
Secondary
Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation
The number of participants maintaining a durable graft 12 months after transplantation. A durable graft was defined as maintenance of normal blood counts: PLT \>50\*10\^9/L without transfusion for at least 2 weeks prior to the visit; hemoglobin level \>= 10 g/dL with no erythropoietin or transfusions for at least 1 month prior to the visit; and absolute neutrophil count (ANC) \> 1,000 (1\*10\^9/L) with no G-CSF for at least 1 week prior to the visit.
Time frame: Approximately 13 months (12 months post transplant )
Population: Participants who received autologous stem cell transplantation and were evaluable 12 months post transplant. The 3 participants who did not have durable grafts included 2 participants whose PLT level never recovered to \>50\*10\^9/L and 1 who had low hemoglobin at the 12-month visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation | 44 Participants |
| Hodgkin's Disease | Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation | 14 Participants |
| Multiple Myeloma | Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation | 7 Participants |
| All Patients | Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation | 65 Participants |
Secondary
Number of Participants With Non-Hodgkin's Lymphoma (NHL) Who Had Evidence of Tumor Cell Mobilization After G-CSF or Plerixafor Administration
The number of participants with Bcl2 translocation in post-treatment samples.
Time frame: Up to Day 7
Population: NHL participants with known follicular or transformed (follicular to diffuse large cell) lymphoma who provided samples for tumor cell mobilization analysis.~Outcome is not reported because there were insufficient samples for analysis.
Secondary
Time to Maximum Plasma Concentration (Tmax) on Day 4
Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data
Time frame: Day 4 (following first plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Time to Maximum Plasma Concentration (Tmax) on Day 4 | 0.500 Hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) on Day 7
Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data
Time frame: Day 7 (following fourth plerixafor administration)
Population: Participants who provided blood samples for pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hodgkin's Lymphoma | Time to Maximum Plasma Concentration (Tmax) on Day 7 | 0.500 Hours |