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AMD3100 (Plerixafor) Added to a Mobilizing Regimen of Granulocyte-colony Stimulating Factor (G-CSF) to Increase the Number of Peripheral Blood Stem Cells (PBSCs) in Patients With Hodgkin's Disease

10 februari 2014 bijgewerkt door: Genzyme, a Sanofi Company

Treatment With AMD3100 Added to a Mobilizing Regimen of G-CSF to Increase the Number of Peripheral Blood Stem Cells in Patients With Hodgkin's Disease

Participants with Hodgkin's Disease (HD) who have been treated with cyto-reductive chemotherapy, who are to undergo autologous stem cell transplantation, and who meet the inclusion/exclusion criteria are eligible to enter this efficacy, safety and pharmacokinetic (PK) study. The only changes to the standard of care is the addition of plerixafor to a granulocyte-colony stimulating factor (G-CSF) mobilization regimen on each day prior to apheresis. The purpose of this protocol is to determine the proportion of participants who reach a target number of CD34+ stem cells (≥5*10^6 cells/kg) after hematopoietic stem cell mobilization with G-CSF and plerixafor. Safety and PK parameters are also collected.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Participants with HD who have been treated with cyto-reductive chemotherapy, who are to undergo autologous stem cell transplantation, and who meet the inclusion/exclusion criteria are eligible to enter this study. The only changes to the standard of care is the addition of plerixafor to a G-CSF mobilization regimen on the day prior to apheresis and the collection of blood samples for pharmacokinetic (PK) analysis and pharmacodynamics (PD) analysis by CD34+ fluorescence-activated cell sorting (FACS) analysis. Blood samples for PK and CD34+ FACS analyses will be obtained prior to and after the first dose of plerixafor. Participants will undergo mobilization with G-CSF (10 µg/kg daily) and will receive plerixafor (240 µg/kg) on each day prior to apheresis. Participants will be apheresed for up to 5 consecutive days in order to collect the target number of CD34+ stem cells, (≥5*10^6 cells/kg). 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 plus plerixafor mobilization regimen. In the event that a sufficient number of cells for transplantation are not obtained from the collection, cells may be retained and pooled for transplantation at the investigator's discretion.

The primary endpoint is the proportion of HD participants who collect ≥5*10^6 CD34+ cells/kg with this mobilization regimen. The secondary endpoints include the safety of this mobilization regimen, the proportion of participants who collect ≥2*10^6 CD34+ cells/kg, the change in CD34+ cells circulating in the peripheral blood after a dose of plerixafor, and the number of days of apheresis required to obtain ≥5*10^6 CD34+ cells/kg. In addition, success of the transplantation will be evaluated by measuring the time to engraftment of PMNs and PLTs. Participants will be followed for 12 months to assess transplant durability.

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

22

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Missouri
      • St Louis, Missouri, Verenigde Staten, 63110-1093
        • Washington University School of Medicine,Division of Bone Marrow Transplantation & Leukemia

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Diagnosis of HD eligible for autologous transplantation
  • No more than 3 prior regimens of chemotherapy (Rituximab is not considered chemotherapy for the purpose of this study.)
  • 4 weeks since last cycle of chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • The patient has recovered from all acute toxic effects of prior chemotherapy
  • White blood cell count (WBC) >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)

Exclusion Criteria:

  • A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications
  • Patients who have failed previous collections
  • A residual acute medical condition resulting from prior chemotherapy
  • Hodgkin's disease involving the central nervous system
  • Acute infection
  • Fever (temp >38°C/100.4°F)
  • Patients whose actual body weight exceeds 150% of their ideal body weight
  • History of ventricular arrhythmias
  • History of paresthesias
  • 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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Participants with Hodgkin's Disease (HD)
Participants with Hodgkin's Disease who were eligible for autologous peripheral blood stem cell transplantation.
Geneesmiddel: G-CSF Plus Plerixafor
Randomized participants underwent mobilization with G-CSF 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection. 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 4 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.
Andere namen:
  • AMD3100
  • Mozobil

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
Tijdsspanne: Day 5 up to Day 9
The proportion of total participants who mobilized ≥5*10^6 CD34+ cells/kg based on data from local laboratories.
Day 5 up to Day 9

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Participant Counts of Adverse Events During the Treatment Period
Tijdsspanne: Day 0 - approximately day 38

Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe and life-threatening) and relatedness (5 steps from 'not related' to 'definitely related') to study treatment. Time frame starts on the first day of G-CSF mobilization to the day prior to chemotherapy/ablative treatment in preparation for transplant.

See the separate Serious Adverse Event section for a summary of AEs the investigator assessed as serious.
Day 0 - approximately day 38
Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
Tijdsspanne: Day 5 up to day 9
The proportion of total participants who mobilized ≥2*10^6 CD34+ cells/kg based on data from local laboratories.
Day 5 up to day 9
Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL
Tijdsspanne: Days 4-5 (first dose of plerixafor to apheresis)
The fold increase was measured by fluorescence activated cell sorting (FACS) analysis using local laboratory data and was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL)/(pre-plerixafor dosing PB CD34+ cells/µL).
Days 4-5 (first dose of plerixafor to apheresis)
Participant Counts Grouped by Number of Apheresis Days Required to Collect ≥ 5*10^6 CD34+ Cells/kg
Tijdsspanne: Day 5 up to day 9
Counts of participants grouped by the number of apheresis days needed to collect a target for transplantation of ≥5*10^6 CD34+ cells/kg as determined by local laboratory data.
Day 5 up to day 9
Number of Days Post-Transplantation to Polymorphonuclear Leukocyte (PMN) Engraftment
Tijdsspanne: Up to Month 13 (up to 12 months post transplant)
Median number of days to PMN engraftment following transplantation. Engraftment was defined as PMN counts ≥ 0.5*10^9/L for 3 consecutive days or ≥ 1.0*10^9/L for 1 day. Time to engraftment corresponded to the first day that the criteria were met.
Up to Month 13 (up to 12 months post transplant)
Number of Days Post Transplantation to Platelet (PLT) Engraftment
Tijdsspanne: Up to Month 13 (up to 12 months post transplant)
Median number of days to PLT engraftment following transplantation. Engraftment success was evaluated according to local site practice. Time to engraftment corresponded to the first day that criteria were met.
Up to Month 13 (up to 12 months post transplant)
Number of Participants With a Durable Graft at 12 Months
Tijdsspanne: 13 months
Graft durability was assessed by the Investigator based on complete blood count (CBC) and differential analyses at 12 months post transplantation. A graft was considered durable if blood counts were normal (acceptable) and still met the criteria for PLT and PMN engraftment.
13 months
Maximum Plasma Concentration (Cmax) Following a Single Dose of Plerixafor
Tijdsspanne: Day 4
Maximum plasma concentration (Cmax) of plerixafor following the first single dose of 240 ug/kg plerixafor administered.
Day 4
Time to Maximum Plasma Concentration (Tmax) Following a Single Dose of Plerixafor
Tijdsspanne: Day 4
Time to maximum plasma concentration (Tmax) of plerixafor following the first single dose of 240 ug/kg plerixafor was determined from direct observation of the data.
Day 4
Half-life (T1/2) Following a Single Dose of Plerixafor
Tijdsspanne: Day 4
Plasma elimination half-life (T1/2) following a single dose of 240 ug/kg plerixafor.
Day 4
Area Under the Plasma Concentration-time Curve From 0 to 10 Hours (AUC0-10) Following a Single Dose of Plerixafor
Tijdsspanne: Days 4-5
Area under the plasma concentration-time curve from 0 to 10 hours (AUC0-10) following the first single dose of 240 ug/kg plerixafor.
Days 4-5
Apparent Clearance (CL/F) of Single-dose Plerixafor
Tijdsspanne: Day 4-5
Apparent clearance was calculated the mean dose of plerixafor divided by the area under the plasma concentration-time curve from 0 hours to infinity (AUC0-inf).
Day 4-5
Apparent Volume of Distribution (Vz/F) Following a Single-dose of Plerixafor
Tijdsspanne: Day 4
The volume of distribution (Vz/F) was calculated as apparent clearance divided by the terminal elimination rate constant.
Day 4

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Genzyme, a Sanofi Company

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 november 2004

Primaire voltooiing (Werkelijk)

1 oktober 2006

Studie voltooiing (Werkelijk)

1 januari 2008

Studieregistratiedata

Eerst ingediend

2 november 2006

Eerst ingediend dat voldeed aan de QC-criteria

2 november 2006

Eerst geplaatst (Schatting)

6 november 2006

Updates van studierecords

Laatste update geplaatst (Schatting)

13 maart 2014

Laatste update ingediend die voldeed aan QC-criteria

10 februari 2014

Laatst geverifieerd

1 februari 2014

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • AMD3100-2106

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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