Clinical trial NCT00396266: AMD3100 (Plerixafor) Given to NHL and MM Patients to Increase the Number of PBSCs When Given a Mobilizing Regimen of G-CSF
Official title: Treatment With AMD3100 in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients to Increase the Number of Peripheral Blood Stem Cells When Given a Mobilizing Regimen of G-CSF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkin's Lymphoma
Multiple Myeloma
stem cell mobilization
AMD3100
autologous transplantation
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: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety and efficacy of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Efficacy outcomes include evaluation of fold increase in circulating CD34+ cells from just before the first plerixafor injection to 10-11 hours post plerixafor (just before apheresis) and assessment of successful polymorphonuclear leukocyte (PMN) engraftment after transplantation. Data from this protocol will assist in the determination of the dosing schedule for future studies.

Detailed description: Participants with NHL and MM who have undergone prior cyto-reductive chemotherapy, are to be autologously transplanted, and meet the inclusion/exclusion criteria are eligible to enter the study. The only change to the standard of care is the addition of plerixafor to a granulocyte colony-stimulating factor (G-CSF) mobilization regimen on the day prior to apheresis. Participants will undergo mobilization with G-CSF (10 mcg/kg each day) and will receive plerixafor (240 mcg/kg) in the evening prior to apheresis. Participants will undergo apheresis for up to 5 consecutive days in order to collect the target number of CD34+ stem cells (≥ 5\*10\^6 CD34+ cells/kg for either single or tandem transplant). 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 and plerixafor mobilization regimen. The increase in CD34+ cells in the peripheral blood from the time of the plerixafor dose to just prior to apheresis and the number of CD34+ cells in the apheresis product will be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN). A subpopulation will have pharmacokinetic and pharmacodynamic analysis done.

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 non-Hodgkin's lymphoma (NHL) or multiple myoloma (MM) eligible for autologous transplantation
* No more than 3 prior regimens of chemotherapy
* More than 4 weeks since last cycle of chemotherapy. Patient recovered from all acute toxic effects of prior chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* White blood cell (WBC) count \>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) type 1
* Women of child bearing potential agreed to use an approved form of contraception.

Exclusion Criteria:

* • Patients who have failed previous collections

  * Brain metastases or carcinomatous meningitis
  * History of ventricular arrhythmias
  * A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications
  * A residual acute medical condition resulting from prior chemotherapy
  * Acute infection
  * Fever (temp \>38°C/100.4°F)
  * Patients whose actual body weight exceeds 150% of their ideal body weight
  * History of paresthesias (at least Grade 2)
  * 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
  * Positive pregnancy test in female patients
  * Lactating females
  * Patients of child-bearing potential unwilling to implement adequate birth control.
  * Patients who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.

Primary outcomes:
measure: Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)
timeFrame: Day 1 to approximately Day 38 (before start of chemotherapy)
Secondary outcomes:
measure: Number of Participants Who Had a ≥ 2-fold Increase in Circulating CD34+ Cells
timeFrame: Time 0 to 11 hours after the first dose of plerixafor
measure: Number of Transplants Resulting In Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post-Transplant
timeFrame: 2 months
measure: Tumor Cell Mobilization in Non-Hodgkin's Lymphoma (NHL) Participants Following Plerixafor Treatment
timeFrame: Prior to the first (Day 4) and last dose of plerixafor, immediately prior to each apheresis, and 24 hours after the last apheresis.
measure: Single-dose Maximum Observed Concentration of Plerixafor (Cmax)
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose.
measure: Single-dose Time to Maximum Concentration of Plerixafor (Tmax)
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose
measure: Single-dose Half-life of Plerixafor (T1/2)
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose.
measure: Single-dose Area Under the Concentration-time Curve of Plerixafor From Time 0 to 10 Hours Post-dose (AUC0-10)
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose.
measure: Single-dose Apparent Clearance of Plerixafor (CL/F)
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose.
measure: Single-dose Apparent Volume of Distribution of Plerixafor (Vz/F) in NHL and MM Patients
timeFrame: Day 5 - 0 to 10 hours post-first plerixafor dose.
measure: Maximum Fold Increase in Peripheral Blood CD34+ Cells From Baseline Following Initial Administration of Plerixafor
timeFrame: Day 4 (10 hours post first plerixafor dose)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital, BC Cancer Agency
state: British Columbia
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References:
citation: Stewart DA, Smith C, MacFarland R, Calandra G. Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biol Blood Marrow Transplant. 2009 Jan;15(1):39-46. doi: 10.1016/j.bbmt.2008.10.018.