Clinical trial NCT00322842: Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients
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: Lymphoma, Non-Hodgkin
Multiple Myeloma
Keywords: Non-Hodgkin's lymphoma
Multiple Myeloma
Stem cell mobilization
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: AnorMED
First posted: 2006-05-08
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety of plerixafor and other outcomes that are purely exploratory in nature. One other pre-specified outcome is to evaluate an interval of 10-11 hours between dosing with plerixafor and the beginning of apheresis to determine if there will be at least a 2-fold increase in circulating CD34+ cells. Data from this protocol will assist in the determination of the dosing schedule for future studies.

Detailed description: Participants with non-Hodgkin's lymphoma and multiple myeloma who have undergone prior cyto-reductive chemotherapy and are to be autologously transplanted will be treated with a combination of plerixafor and granulocyte colony-stimulating factor (G-CSF) mobilization regimen on the day prior to apheresis. The only change to standard of European care is the addition of plerixafor to a G-CSF mobilizing regimen. Participants will undergo mobilization with G-CSF (10 µg/kg each day) and on each day prior to apheresis will receive plerixafor (240 µg/kg). Participants will undergo apheresis for up to 5 consecutive days in order to collect the target number of (≥ 5\*10\^6) CD34+ stem cells/kg. Participants will be transplanted with cells obtained from the G-CSF and plerixafor mobilization regimen. The number of CD34+ cells mobilized in the peripheral blood from the time of the plerixafor dose to just prior to apheresis and those harvested in the apheresis product will be measured. The number of apheresis sessions required to obtain ≥ 5\*10\^6 CD34+ cells/kg will also be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of poly-morphonuclear leukocytes (PMN) and platelets (PLT). Participants will be followed for durability of their transplant for 12 months following transplantation.

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
* Negative for human immunodeficiency virus (HIV)
* Women of child bearing potential who 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
* History of paresthesias
* 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
* 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: Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor
timeFrame: Days 4-5 (first dose of plerixafor to apheresis)
measure: Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant
timeFrame: 2 months
measure: Increase in Peripheral Blood (PB) CD34+ Cells From Steady-state Hematopoiesis to Pre-leukapheresis in G-CSF+Plerixafor Treated Participants Compared to Historical Controls Treated With G-CSF Alone or Chemotherapy and G-CSF
timeFrame: up to day 8
Other outcomes:
measure: Median Cumulative Number of CD34+ Cells Collected During Apheresis
timeFrame: Days 5-8
measure: Number of Transplants in Which Participants Achieved Platelet (PLT) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant
timeFrame: 2 months
measure: Number of Participants With Durable Engraftment 12 Months After Transplantation
timeFrame: Approximately 13 months (12 months post-transplant )
Locations:
city: Cologne
country: Germany
facility: University of Cologne
city: Dresden
country: Germany
facility: Carl Gustav Carus University Hospital
city: Heidelberg
country: Germany
facility: University of Heidelberg
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Fruehauf S, Seeger T, Maier P, Li L, Weinhardt S, Laufs S, Wagner W, Eckstein V, Bridger G, Calandra G, Wenz F, Zeller WJ, Goldschmidt H, Ho AD. The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with specific gene expression characteristics. Exp Hematol. 2006 Aug;34(8):1052-9. doi: 10.1016/j.exphem.2006.06.003.
citation: Fruehauf S, Ehninger G, Hubel K, Topaly J, Goldschmidt H, Ho AD, Muller S, Moos M, Badel K, Calandra G. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin's lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant. 2010 Feb;45(2):269-75. doi: 10.1038/bmt.2009.142. Epub 2009 Jul 13.
citation: Fruehauf S, Veldwijk MR, Seeger T, Schubert M, Laufs S, Topaly J, Wuchter P, Dillmann F, Eckstein V, Wenz F, Goldschmidt H, Ho AD, Calandra G. A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy. 2009;11(8):992-1001. doi: 10.3109/14653240903121245.