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

This study has been completed.
Sponsor:
Collaborator:
AnorMED
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00322842
First received: May 4, 2006
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Multiple Myeloma
Drug: G-CSF Plus Plerixafor
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Day 1 to approximately Day 38 (before start of chemotherapy) ] [ Designated as safety issue: Yes ]
    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').


Secondary Outcome Measures:
  • Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor [ Time Frame: Days 4-5 (first dose of plerixafor to apheresis) ] [ Designated as safety issue: No ]
    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)

  • 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 [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: up to day 8 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Median Cumulative Number of CD34+ Cells Collected During Apheresis [ Time Frame: Days 5-8 ] [ Designated as safety issue: No ]
    Median total number of CD34+ cells collected during apheresis as measured by a central lab.

  • 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 [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Durable Engraftment 12 Months After Transplantation [ Time Frame: Approximately 13 months (12 months post-transplant ) ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: September 2004
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Non-Hodgkin's Lymphoma (NHL)
Participants with NHL were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
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.
Other Names:
  • Mozobil
  • AMD3100
Experimental: Multiple Myeloma (MM)
Participants with MM were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
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.
Other Names:
  • Mozobil
  • AMD3100

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322842

Locations
Germany
University of Cologne
Cologne, Germany
Carl Gustav Carus University Hospital
Dresden, Germany
University of Heidelberg
Heidelberg, Germany
Sponsors and Collaborators
Genzyme, a Sanofi Company
AnorMED
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Publications:
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00322842     History of Changes
Other Study ID Numbers: AMD3100-EU21
Study First Received: May 4, 2006
Results First Received: October 30, 2010
Last Updated: February 10, 2014
Health Authority: Germany:Bundesinstitut für Arzneimittel und Medizinprodukte

Keywords provided by Sanofi:
Non-Hodgkin's lymphoma
Multiple Myeloma
Stem cell mobilization

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lenograstim
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014