Intravenous AMD3100 for Collection of Autologous Peripheral Blood Stem Cells in Patients With Lymphoma

January 26, 2017 updated by: Washington University School of Medicine

A Phase I/II Study of Intravenous AMD3100 Added to a Mobilization Regimen of G-CSF to Increase the Number of Autologous Peripheral Blood Stem Cells Collected From Patients With Lymphoma

This study will evaluate the safety and efficacy of intravenous AMD3100 added to a standard G-CSF mobilization regimen of patients undergoing autologous stem cell transplantation for lymphoma.

The investigators hypothesize that after stem cell mobilization with G-CSF plus IV AMD3100, a significantly higher proportion of lymphoma patients will collect ≥ 2 x 10E6 CD34+ cells/kg.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Autologous stem cell transplantation (ASCT) is indicated for patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) who have primary progressive disease or who relapse after a chemotherapy-induced complete remission. For these patients, as for other patients undergoing autologous transplantation, the number of CD34+ cells collected is a reliable predictor of neutrophil and platelet (PLT) engraftment after transplantation.

AMD3100 (plerixafor) is a promising new mobilizing agent that has demonstrated efficacy in patients with NHL, HL, and multiple myeloma (MM). Although efficacious, the subcutaneous dosing of AMD3100 requires that patients receive the drug in the evening prior to apheresis, which can present logistical problems. Intravenous dosing of AMD3100 may result in a faster rise in peripheral CD34+ cell count, so that the drug can be administered the same day as apheresis. Intravenous dosing may also increase the peak CD34+ cell count, improving the number of CD34+ cells collected via apheresis.

This Phase I/II study will evaluate the safety and efficacy of intravenous AMD3100 added to the standard G-CSF mobilization regimen of patients undergoing autologous stem cell transplantation for Hodgkin and non-Hodgkin lymphomas.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18 to 75 years
  • Diagnosis of HL or NHL eligible for autologous transplantation
  • 30 days since last cycle of chemotherapy
  • ECOG performance status of 0 or 1
  • The patient has recovered from all acute toxic effects of prior chemotherapy
  • WBC >3.0 X 109/l
  • Absolute PMN count >1.5 X 109/l
  • PLT count >100 X 109/l
  • Serum creatinine ≤ 2.2 mg/dl
  • AST (SGOT), ALT (SGPT) and total bilirubin < 2X upper limit of normal (ULN)
  • Left ventricle ejection fraction > 45% (by ECHO or MUGA scan)
  • FEV1 > 60% of predicted or DLCO > 45% of predicted
  • Negative for HIV on standard transplant workup
  • Signed informed consent

  • Are surgically or biologically sterile or willing to practice acceptable birth control, as follows:

    • Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence.
    • Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period

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
  • Acute infection
  • Fever (temp >38C/100.4F) on the day of start of treatment
  • 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 150% of their ideal body weight
  • History of ventricular arrhythmias
  • 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 phase
  • Patients who have deterioration of their clinical status or laboratory parameters between the time of enrollment and transplantation 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1

240 µg/kg SC AMD3100 Day -5

10 µg/kg SC G-CSF Day -4 thru Day -1

160 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1

Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached)
Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
Procedure: Apheresis
Other Names:
  • Leukopheresis
Drug: AMD3100
Other Names:
  • Plerixafor
Experimental: Cohort 2

240 µg/kg SC AMD3100 Day -5

10 µg/kg SC G-CSF Day -4 thru Day -1

240 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1

Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached)
Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
Procedure: Apheresis
Other Names:
  • Leukopheresis
Drug: AMD3100
Other Names:
  • Plerixafor
Experimental: Cohort 3

240 µg/kg SC AMD3100 Day -5

10 µg/kg SC G-CSF Day -4 thru Day -1

320 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1

Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached)
Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
Procedure: Apheresis
Other Names:
  • Leukopheresis
Drug: AMD3100
Other Names:
  • Plerixafor
Experimental: Cohort 4

240 µg/kg SC AMD3100 Day -5

10 µg/kg SC G-CSF Day -4 thru Day -1

400 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1

Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached)
Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
Procedure: Apheresis
Other Names:
  • Leukopheresis
Drug: AMD3100
Other Names:
  • Plerixafor
Experimental: Phase II

240 µg/kg SC AMD3100 Day -5

10 µg/kg SC G-CSF Day -4 thru Day -1

MTD as determined in Phase I IV AMD3100 and 10 µg/kg SC G-CSF Day 1

Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached)
Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
Procedure: Apheresis
Other Names:
  • Leukopheresis
Drug: AMD3100
Other Names:
  • Plerixafor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of IV AMD3100 + G-CSF in Mobilization of Peripheral Blood Stem Cell in Patients With Lymphoma (Phase I Only)
Time Frame: 7 days from first dose of IV AMD3100
  • MTD: the highest dose level of AMD3100 at which ≤ 1 of 6 participants experience a dose limiting toxicity (DLT). The MTD will be the Phase II dose.
  • DLT: selected grade III or higher (hematologic, cardiac, pulmonary, hepatobiliary/pancreatic, renal, or CNS) not attributable to any other cause.
7 days from first dose of IV AMD3100
Number of Participants Who Experienced Dose Limiting Toxicities in Phase I Portion of Study
Time Frame: 7 days from first dose of IV AMD3100
Dose limiting toxicity: selected grade III or higher (hematologic, cardiac, pulmonary, hepatobiliary/pancreatic, renal, or CNS) not attributable to any other cause.
7 days from first dose of IV AMD3100

Secondary Outcome Measures

Outcome Measure
Time Frame
Kinetics of Stem Cell Mobilization Using IV AMD3100 as Measured by Median Fold Change in the Number of CD34+ Cells After AMD3100 IV Administration
Time Frame: From baseline to Day 1
From baseline to Day 1
Pharmacodynamic Response to a Dose of SC AMD3100 as Measured by Mean Percentage of the Circulating CD34+ Count With the 34+RA-123+/- Phenotype
Time Frame: 1 year
1 year
Toxicity of the Combination IV AMD3100 and G-CSF to Mobilize ≥ 2 x 106 CD34+ Cells/kg as Measured by Number of Participants Who Experience Grade 3 or Higher Adverse Event Broken Down by Adverse Event
Time Frame: 30 days post transplant
30 days post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Amanda F. Cashen, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

August 11, 2008

First Submitted That Met QC Criteria

August 11, 2008

First Posted (Estimate)

August 13, 2008

Study Record Updates

Last Update Posted (Actual)

March 9, 2017

Last Update Submitted That Met QC Criteria

January 26, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-0897 / 201105349

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma, Non-Hodgkin

Clinical Trials on G-CSF

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kazakhstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe