Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

June 5, 2017 updated by: Washington University School of Medicine

A Phase I/II Study Evaluating the Safety and Efficacy of AMD3100 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies

The purpose of this study is to determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Study Type

Interventional

Enrollment (Actual)

92

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
      • Saint 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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Donor criteria:

  • Donor is 18 to 70 years of age inclusive

  • If female and of child-bearing age, must be:

    • non-pregnant,
    • not breast feeding and
    • using adequate contraception
  • Donor is a 6/6 HLA-matched sibling willing to donate peripheral blood stem cell for transplant
  • Donor must be willing to provide written informed consent.
  • Adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
  • Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation)
  • Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis

  • Adequate neurologic function as defined by:

    • No evidence of a severe central or peripheral neurologic abnormality.
    • No history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication
  • Must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test.
  • Must have an ECOG performance status of 0 or 1
  • Must demonstrate ability to be compliant with study regimen.
  • Must not have an active infection at the time of study entry
  • Not have active alcohol or substance abuse within 6 months of study entry
  • Not currently enrolled in another investigational agent study
  • Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation

Recipient criteria:

  • 18 to 65 years of age inclusive
  • Willing and has a 6/6 HLA-matched sibling willing to donate PBSC for transplant
  • Provide signed informed consent

  • If female and of child-bearing age, must be:

    • non-pregnant,
    • not breast feeding, and
    • using adequate contraception

Patient must have one of the following diagnoses:

  • AML in 1st or subsequent remission or in relapse
  • ALL in 1st or subsequent remission or in relapse
  • MDS and intermediate 1 or 2, or high risk by the International Prognostic Scoring System
  • CML in accelerated or second chronic phase
  • NHL or HD in 2nd or greater complete remission, partial remission,or refractory relapse
  • CLL Rai Stage 2-4, failing at least 2 prior regimens
  • MM Stage 2-3
  • Adequate cardiac function with a left ventricular ejection fraction ≥ 40%

  • Adequate pulmonary function defined as:

    • No severe or symptomatic restrictive or obstructive lung disease, and
    • formal pulmonary function testing showing an forced expiratory volume at 1 second (FEV1) ≥50% of predicted and a diffusion capacity of the lung for carbon monoxide (DLCO) ≥40% of predicted, corrected for hemoglobin
  • Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation)
  • Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis
  • Adequate neurologic function as defined by no evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous central nervous system tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain
  • No evidence of active infection at the time of the transplant preparative regimen or at the time of transplantation
  • Patient must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test
  • ECOG performance status of 0 or 1
  • Must demonstrate ability to be compliant with medical regimen
  • Not have active alcohol or substance abuse within 6 months of study entry
  • Not be concurrently enrolled on another study involving an investigational agent
  • Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Subcutaneous (SC) Treatment Plan - Donor
  • Day 1: Mobilization with 240 mcg/kg SC AMD3100 and leukopheresis
  • If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.
Drug: AMD3100
Other Names:
  • Plerixafor
Experimental: Intravenous (IV) Treatment Plan - Donor
  • Day -3: Mobilization with 80-480 mcg/kg/day IV AMD3100 and PK analysis
  • Day 1: Mobilization with 240 mcg/kg/day SC AMD3100 and leukopheresis
  • If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.
Drug: AMD3100
Other Names:
  • Plerixafor
Other: Recipients

  • Conditioning Regimen

    • Cyclophosphamide 60mg/kg/day on Days -3 and -2
    • TBI 550cGy on Day -1

  • GVHD prophylaxis

    *Cyclosporin 3.0mg/kg/day beginning on Day -1 then tapered through Day +100

  • PBSC transplant on Day 0
Procedure: Stem Cell Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only)
Time Frame: Day 1-3
-Defined as the proportion of donors collecting >2.0x106 CD34+ cells/kg [recipient weight]
Day 1-3
Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only)
Time Frame: By Day 100 after transplant
-Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria
By Day 100 after transplant
Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only)
Time Frame: Day +21
-Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir
Day +21

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)
Time Frame: Between Day +100 and +365 post-transplant
-Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria
Between Day +100 and +365 post-transplant
Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only)
Time Frame: 100 days after transplant
-Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause
100 days after transplant
Quality of Life During Stem Cell Mobilization (Recipients Only)
Time Frame: 48-72 hours after last dose of AMD3100
48-72 hours after last dose of AMD3100
Proportion of Donors Who Experience Infusional Toxicity (Donor Only)
Time Frame: Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
-Defined as hypersensitivity reactions. Evaluated by physical exam, blood pressure, heart rate, respirations and temperature one hour prior to the infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours post-infusion
Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax
Time Frame: 0 to 24 hours after dose of IV AMD3100
-Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion
0 to 24 hours after dose of IV AMD3100
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity
Time Frame: 0 to 24 hours after dose of IV AMD3100
-Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion
0 to 24 hours after dose of IV AMD3100

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: John F. DiPersio, M.D., Ph.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

May 1, 2004

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

October 17, 2005

First Submitted That Met QC Criteria

October 17, 2005

First Posted (Estimate)

October 18, 2005

Study Record Updates

Last Update Posted (Actual)

June 6, 2017

Last Update Submitted That Met QC Criteria

June 5, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-0349

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.

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