Clinical trial NCT00396201: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin's Disease
Keywords: Hodgkin's Disease
Stem cell mobilization
apheresis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-11-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
timeFrame: Day 5 up to Day 9
Secondary outcomes:
measure: Overall Participant Counts of Adverse Events During the Treatment Period
timeFrame: Day 0 - approximately day 38
measure: Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
timeFrame: Day 5 up to day 9
measure: Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL
timeFrame: Days 4-5 (first dose of plerixafor to apheresis)
measure: Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg
timeFrame: Day 5 up to day 9
measure: Number of Days Post-Transplantation to Polymorphonuclear Leukocyte (PMN) Engraftment
timeFrame: Up to Month 13 (up to 12 months post transplant)
measure: Number of Days Post Transplantation to Platelet (PLT) Engraftment
timeFrame: Up to Month 13 (up to 12 months post transplant)
measure: Number of Participants With a Durable Graft at 12 Months
timeFrame: 13 months
measure: Maximum Plasma Concentration (Cmax) Following a Single Dose of Plerixafor
timeFrame: Day 4
measure: Time to Maximum Plasma Concentration (Tmax) Following a Single Dose of Plerixafor
timeFrame: Day 4
measure: Half-life (T1/2) Following a Single Dose of Plerixafor
timeFrame: Day 4
measure: Area Under the Plasma Concentration-time Curve From 0 to 10 Hours (AUC0-10) Following a Single Dose of Plerixafor
timeFrame: Days 4-5
measure: Apparent Clearance (CL/F) of Single-dose Plerixafor
timeFrame: Day 4-5
measure: Apparent Volume of Distribution (Vz/F) Following a Single-dose of Plerixafor
timeFrame: Day 4
Other outcomes:
Locations:
city: St Louis
country: United States
facility: Washington University School of Medicine,Division of Bone Marrow Transplantation & Leukemia
state: Missouri
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.