Hodgkin's Disease
Conditions
Keywords
Hodgkin's Disease, Stem cell mobilization, apheresis
Brief summary
Participants with Hodgkin's Disease (HD) who have been treated with cyto-reductive chemotherapy, who are to undergo autologous stem cell transplantation, and who meet the inclusion/exclusion criteria are eligible to enter this efficacy, safety and pharmacokinetic (PK) study. The only changes to the standard of care is the addition of plerixafor to a granulocyte-colony stimulating factor (G-CSF) mobilization regimen on each day prior to apheresis. The purpose of this protocol is to determine the proportion of participants who reach a target number of CD34+ stem cells (≥5\*10\^6 cells/kg) after hematopoietic stem cell mobilization with G-CSF and plerixafor. Safety and PK parameters are also collected.
Detailed description
Participants with HD who have been treated with cyto-reductive chemotherapy, who are to undergo autologous stem cell transplantation, and who meet the inclusion/exclusion criteria are eligible to enter this study. The only changes to the standard of care is the addition of plerixafor to a G-CSF mobilization regimen on the day prior to apheresis and the collection of blood samples for pharmacokinetic (PK) analysis and pharmacodynamics (PD) analysis by CD34+ fluorescence-activated cell sorting (FACS) analysis. Blood samples for PK and CD34+ FACS analyses will be obtained prior to and after the first dose of plerixafor. Participants will undergo mobilization with G-CSF (10 µg/kg daily) and will receive plerixafor (240 µg/kg) on each day prior to apheresis. Participants will be apheresed for up to 5 consecutive days in order to collect the target number of CD34+ stem cells, (≥5\*10\^6 cells/kg). After apheresis, all participants will be treated with high dose chemotherapy in preparation for transplantation. Participants will be transplanted with cells obtained from the G-CSF plus plerixafor mobilization regimen. In the event that a sufficient number of cells for transplantation are not obtained from the collection, cells may be retained and pooled for transplantation at the investigator's discretion. The primary endpoint is the proportion of HD participants who collect ≥5\*10\^6 CD34+ cells/kg with this mobilization regimen. The secondary endpoints include the safety of this mobilization regimen, the proportion of participants who collect ≥2\*10\^6 CD34+ cells/kg, the change in CD34+ cells circulating in the peripheral blood after a dose of plerixafor, and the number of days of apheresis required to obtain ≥5\*10\^6 CD34+ cells/kg. In addition, success of the transplantation will be evaluated by measuring the time to engraftment of PMNs and PLTs. Participants will be followed for 12 months to assess transplant durability. 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
Randomized participants underwent mobilization with G-CSF 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection. 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 4 aphereses or until ≥ 5\*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 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of HD eligible for autologous transplantation * No more than 3 prior regimens of chemotherapy (Rituximab is not considered chemotherapy for the purpose of this study.) * 4 weeks since last cycle of chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * The patient has recovered from all acute toxic effects of prior chemotherapy * White blood cell count (WBC) \>3.0\*10\^9/L * Absolute polymorphonuclear cells (PMN) count \>1.5\*10\^9/L * Platelet (PLT) count \>100\*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) * Left ventricle ejection fraction \>45% by normal echocardiogram or multiple-gated acquisition (MUGA) scan * Forced expiratory volume of the lung in the first second (FEV1) \>60% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO) \>45% of predicted * Negative for human immunodeficiency virus (HIV)
Exclusion criteria
* A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications * Patients who have failed previous collections * A residual acute medical condition resulting from prior chemotherapy * Hodgkin's disease involving the central nervous system * Acute infection * Fever (temp \>38°C/100.4°F) * Patients whose actual body weight exceeds 150% of their ideal body weight * History of ventricular arrhythmias * History of paresthesias * Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Day 5 up to Day 9 | The proportion of total participants who mobilized ≥5\*10\^6 CD34+ cells/kg based on data from local laboratories. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Day 5 up to day 9 | The proportion of total participants who mobilized ≥2\*10\^6 CD34+ cells/kg based on data from local laboratories. |
| Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL | Days 4-5 (first dose of plerixafor to apheresis) | The fold increase was measured by fluorescence activated cell sorting (FACS) analysis using local laboratory data and was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL). |
| Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg | Day 5 up to day 9 | Counts of participants grouped by the number of apheresis days needed to collect a target for transplantation of ≥5\*10\^6 CD34+ cells/kg as determined by local laboratory data. |
| Number of Days Post-Transplantation to Polymorphonuclear Leukocyte (PMN) Engraftment | Up to Month 13 (up to 12 months post transplant) | Median number of days to PMN engraftment following transplantation. Engraftment was defined as 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 the criteria were met. |
| Number of Days Post Transplantation to Platelet (PLT) Engraftment | Up to Month 13 (up to 12 months post transplant) | Median number of days to PLT engraftment following transplantation. Engraftment success was evaluated according to local site practice. Time to engraftment corresponded to the first day that criteria were met. |
| Number of Participants With a Durable Graft at 12 Months | 13 months | Graft durability was assessed by the Investigator based on complete blood count (CBC) and differential analyses at 12 months post transplantation. A graft was considered durable if blood counts were normal (acceptable) and still met the criteria for PLT and PMN engraftment. |
| Overall Participant Counts of Adverse Events During the Treatment Period | Day 0 - approximately day 38 | Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe and life-threatening) and relatedness (5 steps from 'not related' to 'definitely related') to study treatment. Time frame starts on the first day of G-CSF mobilization to the day prior to chemotherapy/ablative treatment in preparation for transplant. See the separate Serious Adverse Event section for a summary of AEs the investigator assessed as serious. |
| Time to Maximum Plasma Concentration (Tmax) Following a Single Dose of Plerixafor | Day 4 | Time to maximum plasma concentration (Tmax) of plerixafor following the first single dose of 240 ug/kg plerixafor was determined from direct observation of the data. |
| Half-life (T1/2) Following a Single Dose of Plerixafor | Day 4 | Plasma elimination half-life (T1/2) following a single dose of 240 ug/kg plerixafor. |
| Area Under the Plasma Concentration-time Curve From 0 to 10 Hours (AUC0-10) Following a Single Dose of Plerixafor | Days 4-5 | Area under the plasma concentration-time curve from 0 to 10 hours (AUC0-10) following the first single dose of 240 ug/kg plerixafor. |
| Apparent Clearance (CL/F) of Single-dose Plerixafor | Day 4-5 | Apparent clearance was calculated the mean dose of plerixafor divided by the area under the plasma concentration-time curve from 0 hours to infinity (AUC0-inf). |
| Apparent Volume of Distribution (Vz/F) Following a Single-dose of Plerixafor | Day 4 | The volume of distribution (Vz/F) was calculated as apparent clearance divided by the terminal elimination rate constant. |
| Maximum Plasma Concentration (Cmax) Following a Single Dose of Plerixafor | Day 4 | Maximum plasma concentration (Cmax) of plerixafor following the first single dose of 240 ug/kg plerixafor administered. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Hodgkin's Disease (HD) Participants with Hodgkin's Disease who were eligible for autologous peripheral blood stem cell transplantation. Participants underwent mobilization with G-CSF (10 µg/kg QD) and received plerixafor (240 µg/kg) on each day prior to apheresis. Participants were apheresed for up to 5 consecutive days in order to collect the target number of CD34+ stem cells, (≥5\*10\^6 cells/kg). | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Participants With Hodgkin's Disease (HD) |
|---|---|
| Age, Continuous | 34.0 years STANDARD_DEVIATION 12.5 |
| Race/Ethnicity, Customized Caucasian | 22 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
The proportion of total participants who mobilized ≥5\*10\^6 CD34+ cells/kg based on data from local laboratories.
Time frame: Day 5 up to Day 9
Population: Intent to treat population which included all participants who received plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Proportion achieving ≥5*10^6 CD34+ cells/kg | 0.68 proportion of participants |
| Participants With Hodgkin's Disease (HD) | Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Proportion not achieving ≥5*10^6 CD34+ cells/kg | 0.32 proportion of participants |
Secondary
Apparent Clearance (CL/F) of Single-dose Plerixafor
Apparent clearance was calculated the mean dose of plerixafor divided by the area under the plasma concentration-time curve from 0 hours to infinity (AUC0-inf).
Time frame: Day 4-5
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Apparent Clearance (CL/F) of Single-dose Plerixafor | 5138 mL/hr | Standard Deviation 2029 |
Secondary
Apparent Volume of Distribution (Vz/F) Following a Single-dose of Plerixafor
The volume of distribution (Vz/F) was calculated as apparent clearance divided by the terminal elimination rate constant.
Time frame: Day 4
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Apparent Volume of Distribution (Vz/F) Following a Single-dose of Plerixafor | 25464 mL | Standard Deviation 9002 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to 10 Hours (AUC0-10) Following a Single Dose of Plerixafor
Area under the plasma concentration-time curve from 0 to 10 hours (AUC0-10) following the first single dose of 240 ug/kg plerixafor.
Time frame: Days 4-5
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Area Under the Plasma Concentration-time Curve From 0 to 10 Hours (AUC0-10) Following a Single Dose of Plerixafor | 3572 ng*hr/mL | Standard Deviation 772 |
Secondary
Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL
The fold increase was measured by fluorescence activated cell sorting (FACS) analysis using local laboratory data and was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL).
Time frame: Days 4-5 (first dose of plerixafor to apheresis)
Population: Intent to treat population which included all participants who received plerixafor and had pre- and post-plerixafor CD34+ cell counts available; 3 participants had missing results data and were not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL | 3.2 ratio | Standard Deviation 1.1 |
Secondary
Half-life (T1/2) Following a Single Dose of Plerixafor
Plasma elimination half-life (T1/2) following a single dose of 240 ug/kg plerixafor.
Time frame: Day 4
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Half-life (T1/2) Following a Single Dose of Plerixafor | 3.5 hours | Standard Deviation 0.7 |
Secondary
Maximum Plasma Concentration (Cmax) Following a Single Dose of Plerixafor
Maximum plasma concentration (Cmax) of plerixafor following the first single dose of 240 ug/kg plerixafor administered.
Time frame: Day 4
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Maximum Plasma Concentration (Cmax) Following a Single Dose of Plerixafor | 831 ng/mL | Standard Deviation 183 |
Secondary
Number of Days Post Transplantation to Platelet (PLT) Engraftment
Median number of days to PLT engraftment following transplantation. Engraftment success was evaluated according to local site practice. Time to engraftment corresponded to the first day that criteria were met.
Time frame: Up to Month 13 (up to 12 months post transplant)
Population: Intent to treat population which included all participants who received plerixafor and had a transplant. One participant's time to engraftment was unknown due to missing lab values.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Number of Days Post Transplantation to Platelet (PLT) Engraftment | 19.0 days | Full Range 3.8 |
Secondary
Number of Days Post-Transplantation to Polymorphonuclear Leukocyte (PMN) Engraftment
Median number of days to PMN engraftment following transplantation. Engraftment was defined as 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 the criteria were met.
Time frame: Up to Month 13 (up to 12 months post transplant)
Population: Intent to treat population which included all participants who received plerixafor and had a transplant.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Number of Days Post-Transplantation to Polymorphonuclear Leukocyte (PMN) Engraftment | 9.0 days | Full Range 1.2 |
Secondary
Number of Participants With a Durable Graft at 12 Months
Graft durability was assessed by the Investigator based on complete blood count (CBC) and differential analyses at 12 months post transplantation. A graft was considered durable if blood counts were normal (acceptable) and still met the criteria for PLT and PMN engraftment.
Time frame: 13 months
Population: Intent to treat population which included all participants who received plerixafor and had a transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Hodgkin's Disease (HD) | Number of Participants With a Durable Graft at 12 Months | 21 participants |
Secondary
Overall Participant Counts of Adverse Events During the Treatment Period
Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe and life-threatening) and relatedness (5 steps from 'not related' to 'definitely related') to study treatment. Time frame starts on the first day of G-CSF mobilization to the day prior to chemotherapy/ablative treatment in preparation for transplant. See the separate Serious Adverse Event section for a summary of AEs the investigator assessed as serious.
Time frame: Day 0 - approximately day 38
Population: Safety population consisting of all participants who received G-CSF and/or plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Relationship - Probably Not Related | 1 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Reporting at least one AE | 17 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Severity - Mild | 5 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Severity - Moderate | 11 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Severity - Severe | 1 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Severity - Life Threatening | 0 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Relationship - Not Related | 2 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Relationship - Possibly Related | 12 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Relationship - Probably Related | 1 participants |
| Participants With Hodgkin's Disease (HD) | Overall Participant Counts of Adverse Events During the Treatment Period | Relationship - Definitely Related | 1 participants |
Secondary
Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg
Counts of participants grouped by the number of apheresis days needed to collect a target for transplantation of ≥5\*10\^6 CD34+ cells/kg as determined by local laboratory data.
Time frame: Day 5 up to day 9
Population: Intent to treat population which included all participants who received plerixafor and achieved a target of ≥5\*10\^6 CD34+cells/kg
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg | 1 day of apheresis | 7 participants | 0.9 |
| Participants With Hodgkin's Disease (HD) | Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg | 2 days of apheresis | 6 participants | — |
| Participants With Hodgkin's Disease (HD) | Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg | 3 days of apheresis | 2 participants | — |
Secondary
Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
The proportion of total participants who mobilized ≥2\*10\^6 CD34+ cells/kg based on data from local laboratories.
Time frame: Day 5 up to day 9
Population: Intent to treat population which included all participants who received plerixafor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Proportion achieving ≥2*10^6 CD34+ cells/kg | 0.95 proportion of participants |
| Participants With Hodgkin's Disease (HD) | Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF | Proportion not achieving ≥2*10^6 CD34+ cells/kg | 0.05 proportion of participants |
Secondary
Time to Maximum Plasma Concentration (Tmax) Following a Single Dose of Plerixafor
Time to maximum plasma concentration (Tmax) of plerixafor following the first single dose of 240 ug/kg plerixafor was determined from direct observation of the data.
Time frame: Day 4
Population: The last nine study participants had pharmacokinetic blood samples taken, as reflected in a protocol amendment. Results include participants from the last nine participants who had the relevant test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Hodgkin's Disease (HD) | Time to Maximum Plasma Concentration (Tmax) Following a Single Dose of Plerixafor | 0.6 hours | Standard Deviation 0.4 |