AMD31002106: AMD3100 Added to a Mobilizing Regimen of G-CSF to Increase the Number of PBSCs in Patients with Hodgkin’s Disease

This study is ongoing, but not recruiting participants.

Sponsored By:	Genzyme AnorMED Corporation, a wholly owned subsidiary of Genzyme
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00396201

Purpose

Patients 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 study. The only changes to the standard of care is the addition of AMD3100 to a G-CSF mobilization regimen on the day prior to apheresis. Patients will undergo mobilization with G CSF (10 µg/kg QD) and will receive AMD3100 (240 µg/kg) on each day prior to apheresis. Patients will be apheresed for up to 5 consecutive days in order to collect the target number of CD34+ stem cells, (≧5 x 10e6 cells/kg). All patients will be treated with high dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G CSF plus AMD3100 mobilization regimen.

Condition	Intervention	Phase
Hodgkin’s Disease	Drug: AMD3100 Procedure: Stem cell mobilization Drug: G-CSF Procedure: autologous transplantation Procedure: apheresis	Phase II

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

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

Further Study Details:

Primary Outcomes: To determine the proportion of HD patients who collect ≧5 x 10e6 CD34+ cells/kg after; stem cell mobilization with G-CSF plus AMD3100.

Secondary Outcomes: To determine the safety of AMD3100 when added to G-CSF for the mobilization of PBSCs in HD patients undergoing autologous stem cell transplantation; To determine the proportion of HD patients who collect ≧2 x 10e6 CD34+ cells/kg after; stem cell mobilization with G-CSF plus AMD3100; To determine the change in circulating CD34+ cells from time 0 to 10 - 11 hours after a dose of AMD3100; To determine the number of days required to collect ≧5 x10e6 CD34+ cells/kg; To determine the time of PMN and PLT engraftment; To evaluate graft durability at 3, 6, and 12 months after stem cell transplantation; To examine the pharmacokinetics and pharmacodynamics of a single dose of 240 µg/kg AMD3100 administered after 4 days of G-CSF mobilization in patients with HD.

Expected Total Enrollment: 22

Study start: November 2004

Patients 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 study. The only changes to the standard of care is the addition of AMD3100 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+ FACS analysis). Blood samples for PK and CD34+ FACS analyses will be obtained prior to and after the first dose of AMD3100. Patients will undergo mobilization with G CSF (10 µg/kg QD) and will receive AMD3100 (240 µg/kg) on each day prior to apheresis. Patients will be apheresed for up to 5 consecutive days in order to collect the target number of CD34+ stem cells, (≧5 x 10e6 cells/kg). All patients will be treated with high dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G CSF plus AMD3100 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 patients who collect ≧5 x 10e6 CD34+ cells/kg with this mobilization regimen. The secondary endpoints include the safety of this mobilization regimen, the proportion of patients who collect ≧2 x 10e6 CD34+ cells/kg, the change in CD34+ cells circulating in the peripheral blood after a dose of AMD3100, and the number of days of apheresis required to obtain ≧5 x 10e6 CD34+ cells/kg. In addition, success of the transplantation will be evaluated by measuring the time to engraftment of polymorpho-nuclear leukocytes (PMNs) and platelets (PLTs). Patients will be followed for 12 months to ensure transplant durability.

Eligibility

Ages Eligible for Study: 18 Years - 70 Years

Genders Eligible for Study: Both

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

ECOG performance status of 0 or 1

The patient has recovered from all acute toxic effects of prior chemotherapy

WBC >3.0 X 10e9/l

Absolute PMN count >1.5 x 10e9/l

PLT count >100 x 10e9/l

Serum creatinine ≦2.2 mg/dl

SGOT, SGPT and total bilirubin <2 x upper limit of normal (ULN)

Left ventricle ejection fraction >45% (by normal ECHO or MUGA scan)

FEV₁>60% of predicted or DLCO >45% of predicted

Negative for HIV

Signed informed consent

Women of child bearing potential agree to use an approved form of contraception.

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)

Positive pregnancy test in female patients

Lactating females

Patients of child bearing potential unwilling to implement adequate birth control

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 phase

Patients who have deterioration of their clinical status or laboratory parameters between the time of enrollment and transplantation such that they no longer meet entry criteria may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.

Location Information

United States, Missouri
Washington University School of Medicine, Division of Bone Marrow Transplantation & Leukemia, St Louis, Missouri, 63110-1093, United States

More Information

Study ID Numbers: AMD3100-2106
ClinicalTrials.gov Identifier: NCT00396201
Health Authority: United States: Food and Drug Administration