AMD3100 (Plerixafor) Added to a Mobilizing Regimen of Granulocyte-colony Stimulating Factor (G-CSF) to Increase the Number of Peripheral Blood Stem Cells (PBSCs) in Patients With Hodgkin's Disease

Phase 2

Completed

Conditions: Hodgkin's Disease

Interventions: Drug: G-CSF Plus Plerixafor

Registration Number: NCT00396201

Lead Sponsor: Genzyme, a Sanofi Company

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with Hodgkin's Disease (HD)	G-CSF Plus Plerixafor	Participants with Hodgkin's Disease who were eligible for autologous peripheral blood stem cell transplantation.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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.