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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00241358
First Posted: October 18, 2005
Last Update Posted: June 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
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.

Condition Intervention Phase
Leukemia, Myeloid, Acute Leukemia, Myelogenous, Chronic Leukemia, Lymphoblastic, Acute Lymphocytic Leukemia, Chronic Myelodysplastic Syndromes Multiple Myeloma Lymphoma, Non-Hodgkin Hodgkin Disease Drug: AMD3100 Procedure: Stem Cell Transplant Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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]

  • 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

  • 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


Secondary Outcome Measures:
  • 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

  • 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

  • Quality of Life During Stem Cell Mobilization (Recipients Only) [ Time Frame: 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

  • 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

  • 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


Enrollment: 92
Study Start Date: May 2004
Study Completion Date: February 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Plerixafor
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

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.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00241358


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: John F. DiPersio, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00241358     History of Changes
Other Study ID Numbers: 03-0349
First Submitted: October 17, 2005
First Posted: October 18, 2005
Results First Submitted: April 30, 2017
Results First Posted: June 6, 2017
Last Update Posted: June 6, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:
Plerixafor
Stem cell transplantation
Stem cells
Mobilization

Additional relevant MeSH terms:
Leukemia
Multiple Myeloma
Myelodysplastic Syndromes
Preleukemia
Leukemia, Lymphoid
Hodgkin Disease
Lymphoma, Non-Hodgkin
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Lymphoma
Leukemia, B-Cell