AMD3100 (Plerixafor) With G-CSF in Poor Mobilizing Adult Patients Who Previously Failed Hematopoietic Stem Cell (HSC) Collection/Attempts

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00396331
First received: November 2, 2006
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

This study evaluates the safety, efficacy, and pharmacokinetics (PK) 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 who would benefit from an autologous stem cell transplant but have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests.

The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 (plerixafor) on the evening prior to each day of apheresis.

Efficacy outcomes include quantification of CD34+ cells in the apheresis product and assessment of successful polymorphonuclear leukocyte (PMN) and platelet (PLT) engraftment after transplantation. PK outcomes include analysis of repeated doses of plerixafor.


Condition Intervention Phase
Autologous Stem Cell Transplantation
Drug: G-CSF plus plerixafor
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of AMD3100 (240 µg/kg) Added to a G-CSF Mobilization Regimen in Poor Mobilizing Adult Patients Who Have Previously Failed Stem Cell Collection/Attempts

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period [ Time Frame: Day 1 to approximately day 38 ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').

  • Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF [ Time Frame: Day 5 to Day 11 (up to 7 apheresis) ] [ Designated as safety issue: No ]
    Proportion of participants who reached the target of at least 2*10^6 CD34+ cells/kg collected during up to 7 aphereses.

  • Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF [ Time Frame: Day 5 to Day 11 (up to 7 aphereses) ] [ Designated as safety issue: No ]
    Proportion of participants who reached the target of at least 5*10^6 CD34+ cells/kg collected during up to 7 apheresis.


Secondary Outcome Measures:
  • Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment [ Time Frame: approximately 2 months (1 month post transplant) ] [ Designated as safety issue: No ]
    The number of days from transplantation to successful engraftment as measured by PMN >=0.5*10^9 /L for 3 days or >=1.0*10^9 /L for 1 day.

  • Median Number of Days to Platelet (PLT) Engraftment [ Time Frame: Approximately 2 months (1 month post transplant) ] [ Designated as safety issue: No ]
    The number of days from transplantation to successful engraftment as measured by platelet value of >=20*10^9/L for 7 days without transfusion.

  • Number of Participants With Durable Engraftment 12 Months After Autologous 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 transplantation. A durable graft was defined as maintenance of normal blood counts: PLT >50*10^9/L without transfusion for at least 2 weeks prior to the visit; hemoglobin level >= 10 g/dL with no erythropoietin or transfusions for at least 1 month prior to the visit; and absolute neutrophil count (ANC) > 1,000 (1*10^9/L) with no G-CSF for at least 1 week prior to the visit.

  • Number of Participants With Non-Hodgkin's Lymphoma (NHL) Who Had Evidence of Tumor Cell Mobilization After G-CSF or Plerixafor Administration [ Time Frame: Up to Day 7 ] [ Designated as safety issue: No ]
    The number of participants with Bcl2 translocation in post-treatment samples.

  • Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF [ Time Frame: Day 5 up to Month 6 (up to 7 aphereses in each course of treatment) ] [ Designated as safety issue: No ]
    Number of participants who had at least 2*10^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together.

  • Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF [ Time Frame: Day 5 up to Month 6 (up to 7 aphereses in each course of treatment) ] [ Designated as safety issue: No ]
    Number of participants who had at least 5*10^6 CD34+ cells/kg collected by apheresis during both the first and the second courses of treatment together.

  • Maximum Observed Plasma Concentration (Cmax) on Day 4 [ Time Frame: Day 4 (following first plerixafor administration) ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data.

  • Maximum Observed Plasma Concentration (Cmax) on Day 7 [ Time Frame: Day 7 (following fourth plerixafor administration) ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data.

  • Time to Maximum Plasma Concentration (Tmax) on Day 4 [ Time Frame: Day 4 (following first plerixafor administration) ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data

  • Time to Maximum Plasma Concentration (Tmax) on Day 7 [ Time Frame: Day 7 (following fourth plerixafor administration) ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration (Tmax) of plerixafor following daily doses of 240 µg/kg plerixafor, determined directly from the concentration-time data

  • Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 4 [ Time Frame: Days 4 -5 (following first plerixafor administration) ] [ Designated as safety issue: No ]
    Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule.

  • Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 7 [ Time Frame: Days 7-8 (following fourth plerixafor administration) ] [ Designated as safety issue: No ]
    Area under the steady-state plasma concentration time curve from time zero to the last quantifiable sample after each plerixafor daily dose of 240 µg/kg, determined using the linear trapezoidal rule.


Enrollment: 100
Study Start Date: October 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: G-CSF plus Plerixafor Drug: G-CSF plus plerixafor
Participants underwent mobilization with granulocyte colony-stimulating factor (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 7 aphereses or until ≥ 2*10^6 CD34+ cells/kg were collected.
Other Names:
  • AMD3100
  • Mozobil

Detailed Description:

This is a Phase 2, multicenter, prospective, open-label study. Once 70 patients have enrolled, subsequent patients enrolled should have a diagnosis of lymphoma. Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF) alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests, and who meet the inclusion/exclusion criteria are eligible to receive plerixafor as outlined in this protocol. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of plerixafor on the evening prior to each day of apheresis.

Patients will undergo mobilization with G-CSF (10 µg/kg) for 4 days. On Day 4, plerixafor (240 µg/kg) will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter, such that there is a 10 to 11 hour interval between dosing and the initiation of apheresis. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≥2*10^6 CD34+ cells/kg are collected, whichever occurs first. In addition, the mobilization of NHL tumor cells and the pharmacokinetics of repeat doses of plerixafor will be examined.

After the last apheresis has been completed, or after the patient has collected ≥2*10^6 CD34+ cells/kg, he/she will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with plerixafor mobilization regimen. In the event that the minimum number of ≥2*10^6 cells for transplantation are not obtained from the first mobilization with plerixafor, cells may be retained and pooled for transplantation with those from a second mobilization with plerixafor (or from prior mobilization with other agents), at the investigator's discretion. If a second mobilization with plerixafor is attempted, a minimum rest interval of one week should be allowed between the last apheresis of the first regimen and the first dose of G-CSF of the second. The number of CD34+ cells mobilized in the peripheral blood (PB), collected in the apheresis product, and the number of apheresis sessions performed will be measured. Success of the transplantation will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN) and platelets (PLT). Participants will be assessed for durability of their transplant for 12 months after 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 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible to undergo autologous transplantation
  • Has failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF), chemotherapy and G-CSF or any other conventional therapy including cytokines, chemotherapy and cytokines or bone marrow harvest.
  • Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
  • ≥3 weeks since last cycle of chemotherapy (thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study) NOTE: Although thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study, none are to be administered within 7 days prior to the first dose of G-CSF (see Exclusion Criteria).
  • The patient has recovered from all acute toxic effects of prior chemotherapy
  • White blood cell count (WBC) >2.5*10^9/L
  • Absolute neutrophil count >1.5*10^9/L
  • Platelet count >85*10^9/L
  • Serum creatinine ≤1.5 mg/dl
  • Creatinine clearance >60 ml/min
  • Aspartate aminotransferase (AST), alanine transaminase (ALT) and total bilirubin <2x upper limit of normal (ULN)
  • Left ventricle ejection fraction >45% (by normal echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan)
  • Forced expiratory volume in one minute (FEV1) >60% of predicted or diffusion lung capacity for carbon monoxide (DLCO) ≥45% of predicted
  • No active infection of hepatitis B or C
  • Negative for HIV
  • Signed informed consent
  • Women of child-bearing potential agree to use an approved form of contraception

Exclusion Criteria:

  • Once 70 patients have enrolled, patients with diagnoses other than lymphoma are not eligible (eg, acute myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma).
  • A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications
  • A residual acute medical condition resulting from prior chemotherapy
  • Received Neupogen™, thalidomide, dexamethasone, and/or Velcade™ within 7 days prior to the first dose of G-CSF
  • Brain metastases or carcinomatous meningitis
  • Acute infection
  • Fever (temperature >38°C/100.4°F)
  • Hypercalcaemia (>1 mg/dL above the ULN)
  • Positive pregnancy test in female patients
  • Lactating females
  • Patients of child-bearing potential unwilling to implement adequate birth control
  • 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 protocol or who are currently enrolled in another experimental protocol during the Mobilization phase
  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: NCT00396331

Locations
United States, California
City of Hope National Medical Center`
Duarte, California, United States, 91010
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612-9497
United States, Georgia
Blood & Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Mississippi
University of Mississippi Medical Center, Div of Hematology
Jackson, Mississippi, United States, 39216
United States, Missouri
Kansas City Cancer Centers
Kansas City, Missouri, United States, 64111
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Virginia
Virginia Commonwealth University - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
University of Wisconsin, Blood and Bone Marrow Transplant
Madison, Wisconsin, United States, 53792-5156
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00396331     History of Changes
Other Study ID Numbers: AMD31002112
Study First Received: November 2, 2006
Results First Received: November 2, 2010
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Multiple Myeloma
Non-Hodgkin's Lymphoma
autologous transplantation
AMD3100
stem cell mobilization
plerixafor

Additional relevant MeSH terms:
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014