Clinical trial NCT00395967: AMD3100 (Plerixafor) in Multiple Myeloma (MM) or Non-Hodgkin's Lymphoma (NHL) Patients Predicted to be Unable to Mobilize With G-CSF Alone
Official title: Effect of AMD3100 (240µg/kg) on the Apheresis Yield of CD34+ Cells When Given To Multiple Myeloma or Non-Hodgkin's Lymphoma Patients Predicted to be Unable to Mobilize ≥2 x 10^6 CD34+ Cells in Three Apheresis Days When Given G-CSF Alone
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Lymphoma, Non-Hodgkin's
Keywords: Non-Hodgkin's Lymphoma
Multiple Myeloma
stem cell mobilization
autologous transplantation
AMD3100
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-11-06
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Patients Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor 240 µg/kg and G-CSF for up to 3 Consecutive Days
timeFrame: approximately days 6-9
Secondary outcomes:
measure: Overall Participants Counts of Adverse Events
timeFrame: up to 13 months
measure: The Fold Increase in Peripheral Blood CD34+ Cells Following the First Dose of Plerixafor
timeFrame: Days 5-6
measure: Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment
timeFrame: 2 months
measure: Number of Days to Platelet (PLT) Engraftment
timeFrame: 2 months
measure: Graft Durability at 12 Months After Transplantation
timeFrame: 13 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center - Adult BMT Program
state: North Carolina
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: