Mobilization of Stem Cells With AMD3100 (Plerixafor) and G-CSF in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients

This study has been completed.
Sponsor:
Collaborator:
AnorMED
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00322491
First received: May 4, 2006
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


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 point scale from 'not related' to 'definitely related').


Secondary Outcome Measures:
  • Number of Participants Achieving a Two-Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL Following the First Dose of Plerixafor [ Time Frame: Days 4-5 (first dose of plerixafor to apheresis) ] [ Designated as safety issue: No ]
    The number of participants mobilized with G-CSF + plerixafor injection who have a ≥ 2-fold increase in CD34+ cells. Fold increase was expressed as a ratio. Fold increase = (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.


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

  • 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: 49
Study Start Date: March 2004
Study Completion Date: June 2006
Primary Completion Date: June 2006 (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:
  • AMD3100
  • Mozobil
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:
  • AMD3100
  • Mozobil

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. The number of apheresis sessions required to obtain ≥ 5*10^6 CD34+ cells will also be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of polymorphonuclear 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
  • 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 175% 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: NCT00322491

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
United States, California
UCLA School of Medicine
Loa Angeles, California, United States
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States
United States, Iowa
University of Iowa
Iowa City, Iowa, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
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: NCT00322491     History of Changes
Other Study ID Numbers: AMD3100-2105
Study First Received: May 4, 2006
Results First Received: October 30, 2010
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

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 24, 2014