Lymphoma, Non-Hodgkin's, Multiple Myeloma
Conditions
Keywords
Non-Hodgkin's Lymphoma, Multiple Myeloma, stem cell mobilization, autologous transplantation, AMD3100
Brief summary
This Phase 2 study was designed to assess the safety and hematological activity of AMD3100 (plerixafor) in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) who were predicted to be unable to mobilize ≥2\*10\^6 CD34+ cells/kg within 3 apheresis days. Patients with NHL and MM were eligible to enter the study if they had undergone cyto-reductive chemotherapy, were to undergo autologous transplantation, and met the inclusion/exclusion criteria. The purpose of this protocol was to determine whether plerixafor in combination with Granulocyte Colony Stimulating Factor (G-CSF) can increase the circulating levels of peripheral blood stem cells (PBSCs) in patients whose peripheral CD34+ counts remain low after treatment with G-CSF alone, whether it was safe, and whether transplantation with the apheresis product was successful, as measured by time to engraftment of polymorphonuclear leukocytes (PMNs) and platelets (PLTs).
Detailed description
A Phase 2, single-center, open-label study to assess the safety and hematological activity of plerixafor in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) who were predicted to be unable to mobilize ≥2\*10\^6 CD34+ cells/kg within 3 apheresis days. The only change to the standard of care was the addition of plerixafor to a G-CSF mobilization regimen on the day prior to apheresis. Following screening procedures, eligible patients undergo mobilization with G-CSF (10 µg/kg every day) for 5 days and their peripheral blood (PB) CD34+ cell count was measured on the fifth day. On Day 5, if the patient's peripheral CD34+ cell count was \<5 cells/µl or ≥20 cells/µl, the patient did not enter this study and was treated as per the policy of the study site. On Day 5, if the patient's peripheral CD34+ cell count was 5 to 7 cells/µl (inclusive), the patient did not undergo apheresis that day, but did receive plerixafor (240 µg/kg) that evening and G-CSF followed by apheresis the next morning. The evening dose of plerixafor followed the next morning by G-CSF and apheresis was repeated for up to a total of 3 days of apheresis or until ≥5\*10\^6 cells/kg are collected. On Day 5, if the patient's peripheral CD34+ cell count was 8 to 19 cells/µl (inclusive), then he/she underwent apheresis that day. If this apheresis yield was \<1.3\*10\^6 CD34+ cells/kg, then the patient was predicted to be unlikely to collect ≥2\*10\^6 CD34+ cells/kg in ≥3 days of apheresis and received plerixafor (240 µg/kg) that evening. However, if the apheresis yield on Day 5 was ≥1.3\*10\^6 CD34+ cells/kg, then the patient did not enter the study. The next morning (Day 6), eligible patients received G-CSF (10 µg/kg) and began apheresis approximately 10 to 11 hours after the previous evening plerixafor dose. If the apheresis yield was at least double the apheresis yield on Day 5, then the patient received another 10:00 pm dose of plerixafor and underwent apheresis again the next morning (Day 7) after receiving G-CSF. The evening dose of plerixafor followed the next morning by G-CSF and apheresis was repeated for up to a total of 3 days of apheresis or until ≥5\*10\^6 cells/kg were collected. All patients, after the completion of apheresis procedures (or after ≥5\*10\^6 cells/kg were collected), received high-dose chemotherapy in preparation for transplantation. Patients were transplanted with cells collected after receiving plerixafor with G-CSF. However, if there were insufficient cells, cells collected after receiving plerixafor with G-CSF could be pooled with cells collected after receiving G-CSF alone. Hematological activity of plerixafor was evaluated by assessing the number of CD34+ cells harvested during apheresis. 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
Mobilization with Granulocyte Colony Stimulating Factor (G-CSF) (10 µg/kg once a day) for 5 days. Patients received once daily plerixafor treatment (240 mg/kg) in the evening (10 to 11 hours prior to apheresis) for up to 3 days if peripheral blood CD34+ cell counts on Day 5 met the entry criteria. Morning doses of G-CSF (10 µg/kg) continued throughout apheresis.
Sponsors
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
(Abbreviated List): * Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) * Eligible for autologous transplantation * \<=3 prior regimens of chemotherapy (Rituxan is not considered chemotherapy for the purpose of this study) * \>4 weeks since last cycle of chemotherapy (Rituxan is not considered chemotherapy for the purpose of this study) * Total dose of melphalan ≦200 mg * Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 * White blood cell (WBC) count \>3.0\*10\^9/L prior to first dose of G-CSF * Absolute polymorphonuclear leukocyte (PMN) count \>1.5\*10\^9/L prior to first dose of G-CSF * Platelet (PLT) count \>100\*10\^9/L prior to first dose of granulocyte colony-stimulating factor (G-CSF) * Serum creatinine ≥2.2 mg/dL * SGOT, SGPT and total bilirubin \<2 times upper limit of normal (ULN) * Negative for HIV * CD34+ cell count between 5 and 19 CD34+ cells/ml after 5 days of mobilization with G-CSF alone
Exclusion criteria
(Abbreviated List): * A co-morbid condition which, in the view of the investigator, renders the patient at high risk from treatment complications * Failed previous stem cell collection or collection attempts * A residual acute medical condition resulting from prior chemotherapy * Active brain metastases or carcinomatous meningitis * Active infection requiring antibiotic treatment * Received prior radio-immunotherapy with Zevalin or Bexxar * Received bone-seeking radionuclides (e.g., holmium) * Received thalidomide, dexamethasone, and/or Velcade within 7 days prior to the first dose of G-CSF * History of ventricular arrhythmias, including electrocardiogram (ECG)-documented premature ventricular contractions (PVCs), during the last 3 years * 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 * Had an apheresis yield \>1.3\*10\^6 CD34+ cells/kg on Day 5 (Applicable only to patients who, after 5 days of G-CSF mobilization, have peripheral blood (PB) CD34+ count of 8-19 cells/µl inclusive).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor 240 µg/kg and G-CSF for up to 3 Consecutive Days | approximately days 6-9 | The number of patients with a circulating CD34+ count \>= 5 and \< 20 cells/ml after 5 days of mobilization with G-CSF alone who achieved cumulative apheresis yields of ≥2\*10\^6 CD34+ cells/kg within 3 days of apheresis after receiving G-CSF plus plerixafor. Outcome was based on laboratory results from a central lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Participants Counts of Adverse Events | up to 13 months | Numbers of participants with adverse events (AEs) collected from Day 1 (start of G-CSF Mobilization) to 12 months after transplantation. AEs were reported regardless of relationship to study treatment. The investigator graded each AE using the World Health Organization (WHO) Adverse Event Grading Scale and provided assessments of seriousness and relatedness to study treatment. |
| The Fold Increase in Peripheral Blood CD34+ Cells Following the First Dose of Plerixafor | Days 5-6 | The fold increase was measured by fluorescence activated cell sorting (FACS) analysis and expressed as a ratio. Fold increase = pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL). This study was terminated early and analysis was not done. |
| Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 2 months | The median number of days to PMN engraftment criteria was PMN counts ≥ 0.5\*10\^9/L for 3 consecutive days or ≥ 1.0\*10\^9/L for 1 day. Time to engraftment corresponded to the first day that criteria were met. This study was terminated early and analysis was not done. |
| Number of Days to Platelet (PLT) Engraftment | 2 months | The median number of days to platelet (PLT) engraftment criteria was ≥ 20\*10\^9/L platelets without transfusion for the preceding 7 days. Time to engraftment corresponded to the first day that criteria were met. This study was terminated early and analysis was not done. |
| Graft Durability at 12 Months After Transplantation | 13 months | Participants with durable grafts. Graft durability was assessed by complete blood count (CBC) and differential analysis at 12 months post-transplantation. This study was terminated early and analysis was not done. |
Countries
United States
Participant flow
Recruitment details
Study enrollment began in April 2005 and the study was terminated in August 2006. Target enrollment was 15 patients, however the trial was terminated early after five patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| All Patients Mobilization with Granulocyte Colony Stimulating Factor (G-CSF) (10 µg/kg once a day) for 5 days. Patients received once daily plerixafor treatment (240 mg/kg) in the evening (10 to 11 hours prior to apheresis) for up to 3 days if peripheral blood CD34+ cell counts on Day 5 met the entry criteria. Morning doses of G-CSF (10 µg/kg) continued throughout apheresis. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up Period | Death | 1 |
| Follow-up Period | Lost to Follow-up | 1 |
| Treatment Period | Failed Mobilization | 1 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 52.2 years STANDARD_DEVIATION 11.5 |
| Disease Diagnosis Hodgkin's disease (HD) | 1 participants |
| Disease Diagnosis Multiple Myeloma (MM) | 1 participants |
| Disease Diagnosis Non-Hodgkin's lymphoma (NHL) | 3 participants |
| Race/Ethnicity, Customized Caucasian | 5 participants |
| Sex: Female, Male Female | 2 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 | 5 / 5 |
| serious Total, serious adverse events | 4 / 5 |
Outcome results
Primary
Number of Patients Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor 240 µg/kg and G-CSF for up to 3 Consecutive Days
The number of patients with a circulating CD34+ count \>= 5 and \< 20 cells/ml after 5 days of mobilization with G-CSF alone who achieved cumulative apheresis yields of ≥2\*10\^6 CD34+ cells/kg within 3 days of apheresis after receiving G-CSF plus plerixafor. Outcome was based on laboratory results from a central lab.
Time frame: approximately days 6-9
Population: All patients who received plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Number of Patients Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor 240 µg/kg and G-CSF for up to 3 Consecutive Days | Participants with ≥2*10^6 CD34+ cells/kg | 3 participants |
| All Patients | Number of Patients Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor 240 µg/kg and G-CSF for up to 3 Consecutive Days | Participants with <2*10^6 CD34+ cells/kg | 2 participants |
Secondary
Graft Durability at 12 Months After Transplantation
Participants with durable grafts. Graft durability was assessed by complete blood count (CBC) and differential analysis at 12 months post-transplantation. This study was terminated early and analysis was not done.
Time frame: 13 months
Population: This study was terminated early and analysis was not done.
Secondary
Number of Days to Platelet (PLT) Engraftment
The median number of days to platelet (PLT) engraftment criteria was ≥ 20\*10\^9/L platelets without transfusion for the preceding 7 days. Time to engraftment corresponded to the first day that criteria were met. This study was terminated early and analysis was not done.
Time frame: 2 months
Population: This study was terminated early and analysis was not done.
Secondary
Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment
The median number of days to PMN engraftment criteria was PMN counts ≥ 0.5\*10\^9/L for 3 consecutive days or ≥ 1.0\*10\^9/L for 1 day. Time to engraftment corresponded to the first day that criteria were met. This study was terminated early and analysis was not done.
Time frame: 2 months
Population: This study was terminated early and analysis was not done.
Secondary
Overall Participants Counts of Adverse Events
Numbers of participants with adverse events (AEs) collected from Day 1 (start of G-CSF Mobilization) to 12 months after transplantation. AEs were reported regardless of relationship to study treatment. The investigator graded each AE using the World Health Organization (WHO) Adverse Event Grading Scale and provided assessments of seriousness and relatedness to study treatment.
Time frame: up to 13 months
Population: Safety Population defined as all participants who received G-CSF and/or plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Overall Participants Counts of Adverse Events | Participants Reporting At Least One AE | 5 participants |
| All Patients | Overall Participants Counts of Adverse Events | Participants Reporting a Severe AE | 4 participants |
| All Patients | Overall Participants Counts of Adverse Events | Participants Reporting a Life-threatening AE | 2 participants |
| All Patients | Overall Participants Counts of Adverse Events | AE Relation to Drug: Not Related or Probably Not | 3 participants |
| All Patients | Overall Participants Counts of Adverse Events | AE Relation to Drug: Possibly Related | 2 participants |
| All Patients | Overall Participants Counts of Adverse Events | AE Relation to Drug: Probably or Definitely Relate | 0 participants |
| All Patients | Overall Participants Counts of Adverse Events | Serious Adverse Events | 4 participants |
| All Patients | Overall Participants Counts of Adverse Events | AEs Leading to Discontinuation | 0 participants |
Secondary
The Fold Increase in Peripheral Blood CD34+ Cells Following the First Dose of Plerixafor
The fold increase was measured by fluorescence activated cell sorting (FACS) analysis and expressed as a ratio. Fold increase = pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL). This study was terminated early and analysis was not done.
Time frame: Days 5-6
Population: This study was terminated early and analysis was not done.