Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00322842
• Other study ID #: AMD3100-EU21
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2006
• Last updated: February 10, 2014
• Start date: September 2004
• Est. completion date: February 2007

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany:Bundesinstitut für Arzneimittel und Medizinprodukte
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• G-CSF Plus Plerixafor
Participants underwent mobilization with G-CSF 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection each morning. On the evening of Day 4, participants received a dose of plerixafor 240 µg/kg, administered by SC injection. On Day 5, participants returned to the clinic and received a morning dose of G-CSF 10 µg/kg and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor (within 60 minutes after administration of G-CSF). Participants continued to receive an evening dose of plerixafor followed the next day by a morning dose of G-CSF and apheresis for up to a maximum of 5 aphereses or until = 5*10^6 CD34+ cells/kg were collected.

Locations

Country	Name	City	State
Germany	University of Cologne	Cologne
Germany	Carl Gustav Carus University Hospital	Dresden
Germany	University of Heidelberg	Heidelberg

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	AnorMED

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Fruehauf S, Ehninger G, Hübel K, Topaly J, Goldschmidt H, Ho AD, Müller 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 a — View 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. — View 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 periphera — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Median Cumulative Number of CD34+ Cells Collected During Apheresis	Median total number of CD34+ cells collected during apheresis as measured by a central lab.	Days 5-8	No
Other	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	Participants were monitored for platelet (PLT) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.	2 months	No
Other	Number of Participants With Durable Engraftment 12 Months After Transplantation	The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts.	Approximately 13 months (12 months post-transplant )	No
Primary	Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)	Number of participants with treatment emergent adverse events (TEAEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy (approximately day 38). AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness to study treatment (5 step scale from 'not related' to 'definitely related').	Day 1 to approximately Day 38 (before start of chemotherapy)	Yes
Secondary	Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor	The fold increase was measured using local lab values and is the ratio of post first dose (pre-apheresis) PB CD34+ cells/µL)/pre-plerixafor dosing PB CD34+ cells/µL)	Days 4-5 (first dose of plerixafor to apheresis)	No
Secondary	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	Participants were monitored for polymorphonuclear leukocyte (PMN) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.	2 months	No
Secondary	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	A comparison of the effectiveness in mobilizing peripheral blood CD34+ cells between this study's treatment regimen (G-CSF plus plerixafor) to other treatment options: G-CSF alone, and chemotherapy with G-CSF.	up to day 8	No