AMD3100 (Plerixafor) in Multiple Myeloma (MM) or Non-Hodgkin's Lymphoma (NHL) Patients Predicted to be Unable to Mobilize With G-CSF Alone
AMD3100 (Plerixafor) in Multiple Myeloma (MM) or Non-Hodgkin's Lymphoma (NHL) Patients Predicted to be Unable to Mobilize With G-CSF Alone
This Phase 2 study was designed to assess the safety and hematological activity of AMD3100
 (plerixafor) in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) who were
 predicted to be unable to mobilize ≥2*10^6 CD34+ cells/kg within 3 apheresis days. Patients
 with NHL and MM were eligible to enter the study if they had undergone cyto-reductive
 chemotherapy, were to undergo autologous transplantation, and met the inclusion/exclusion
 criteria.

 The purpose of this protocol was to determine whether plerixafor in combination with
 Granulocyte Colony Stimulating Factor (G-CSF) can increase the circulating levels of
 peripheral blood stem cells (PBSCs) in patients whose peripheral CD34+ counts remain low
 after treatment with G-CSF alone, whether it was safe, and whether transplantation with the
 apheresis product was successful, as measured by time to engraftment of polymorphonuclear
 leukocytes (PMNs) and platelets (PLTs).
A Phase 2, single-center, open-label study to assess the safety and hematological activity of
 plerixafor in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) who were
 predicted to be unable to mobilize ≥2*10^6 CD34+ cells/kg within 3 apheresis days. The only
 change to the standard of care was the addition of plerixafor to a G-CSF mobilization regimen
 on the day prior to apheresis.

 Following screening procedures, eligible patients undergo mobilization with G-CSF (10 µg/kg
 every day) for 5 days and their peripheral blood (PB) CD34+ cell count was measured on the
 fifth day.

 On Day 5, if the patient's peripheral CD34+ cell count was <5 cells/µl or ≥20 cells/µl, the
 patient did not enter this study and was treated as per the policy of the study site.

 On Day 5, if the patient's peripheral CD34+ cell count was 5 to 7 cells/µl (inclusive), the
 patient did not undergo apheresis that day, but did receive plerixafor (240 µg/kg) that
 evening and G-CSF followed by apheresis the next morning. The evening dose of plerixafor
 followed the next morning by G-CSF and apheresis was repeated for up to a total of 3 days of
 apheresis or until ≥5*10^6 cells/kg are collected.

 On Day 5, if the patient's peripheral CD34+ cell count was 8 to 19 cells/µl (inclusive), then
 he/she underwent apheresis that day. If this apheresis yield was <1.3*10^6 CD34+ cells/kg,
 then the patient was predicted to be unlikely to collect ≥2*10^6 CD34+ cells/kg in ≥3 days of
 apheresis and received plerixafor (240 µg/kg) that evening. However, if the apheresis yield
 on Day 5 was ≥1.3*10^6 CD34+ cells/kg, then the patient did not enter the study.

 The next morning (Day 6), eligible patients received G-CSF (10 µg/kg) and began apheresis
 approximately 10 to 11 hours after the previous evening plerixafor dose. If the apheresis
 yield was at least double the apheresis yield on Day 5, then the patient received another
 10:00 pm dose of plerixafor and underwent apheresis again the next morning (Day 7) after
 receiving G-CSF. The evening dose of plerixafor followed the next morning by G-CSF and
 apheresis was repeated for up to a total of 3 days of apheresis or until ≥5*10^6 cells/kg
 were collected.

 All patients, after the completion of apheresis procedures (or after ≥5*10^6 cells/kg were
 collected), received high-dose chemotherapy in preparation for transplantation. Patients were
 transplanted with cells collected after receiving plerixafor with G-CSF. However, if there
 were insufficient cells, cells collected after receiving plerixafor with G-CSF could be
 pooled with cells collected after receiving G-CSF alone.

 Hematological activity of plerixafor was evaluated by assessing the number of CD34+ cells
 harvested during apheresis.

 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.
Inclusion Criteria (Abbreviated List):

 -  Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM)

 -  Eligible for autologous transplantation

 -  <=3 prior regimens of chemotherapy (Rituxan is not considered chemotherapy for the
 purpose of this study)

 -  >4 weeks since last cycle of chemotherapy (Rituxan is not considered chemotherapy for
 the purpose of this study)

 -  Total dose of melphalan ≦200 mg

 -  Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1

 -  White blood cell (WBC) count >3.0*10^9/L prior to first dose of G-CSF

 -  Absolute polymorphonuclear leukocyte (PMN) count >1.5*10^9/L prior to first dose of
 G-CSF

 -  Platelet (PLT) count >100*10^9/L prior to first dose of granulocyte colony-stimulating
 factor (G-CSF)

 -  Serum creatinine ≥2.2 mg/dL

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

 -  Negative for HIV

 -  CD34+ cell count between 5 and 19 CD34+ cells/ml after 5 days of mobilization with
 G-CSF alone

 Exclusion Criteria (Abbreviated List):

 -  A co-morbid condition which, in the view of the investigator, renders the patient at
 high risk from treatment complications

 -  Failed previous stem cell collection or collection attempts

 -  A residual acute medical condition resulting from prior chemotherapy

 -  Active brain metastases or carcinomatous meningitis

 -  Active infection requiring antibiotic treatment

 -  Received prior radio-immunotherapy with Zevalin or Bexxar

 -  Received bone-seeking radionuclides (e.g., holmium)

 -  Received thalidomide, dexamethasone, and/or Velcade within 7 days prior to the first
 dose of G-CSF

 -  History of ventricular arrhythmias, including electrocardiogram (ECG)-documented
 premature ventricular contractions (PVCs), during the last 3 years

 -  Patients who previously received experimental therapy within 4 weeks of enrolling in
 this protocol or who are currently enrolled in another experimental protocol during
 the mobilization phase

 -  Had an apheresis yield >1.3*10^6 CD34+ cells/kg on Day 5 (Applicable only to patients
 who, after 5 days of G-CSF mobilization, have peripheral blood (PB) CD34+ count of
 8-19 cells/µl inclusive).