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

Hodgkin's Disease Clinical Trial

Official title:

Treatment With AMD3100 Added to a Mobilizing Regimen of G-CSF to Increase the Number of Peripheral Blood Stem Cells in Patients With Hodgkin's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00396201
• Other study ID #: AMD3100-2106
• Status: Completed
• Phase: Phase 2
• First received: November 2, 2006
• Last updated: February 10, 2014
• Start date: November 2004
• Est. completion date: January 2008

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 2008
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Disease

Intervention

Drug:
• G-CSF Plus Plerixafor
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.

Locations

Country	Name	City	State
United States	Washington University School of Medicine,Division of Bone Marrow Transplantation & Leukemia	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

References & Publications (1)

Cashen A, Lopez S, Gao F, Calandra G, MacFarland R, Badel K, DiPersio J. A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008 Nov;14(11):1253-61. doi: 10.1016/j.bbmt.2008.08.011. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 5 up to Day 9	No
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.	Day 0 - approximately day 38	Yes
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.	Day 5 up to day 9	No
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).	Days 4-5 (first dose of plerixafor to apheresis)	No
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.	Day 5 up to day 9	No
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.	Up to Month 13 (up to 12 months post transplant)	No
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.	Up to Month 13 (up to 12 months post transplant)	No
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.	13 months	No
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.	Day 4	No
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.	Day 4	No
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.	Day 4	No
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.	Days 4-5	No
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).	Day 4-5	No
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.	Day 4	No