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

Primary Purpose

Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, Leukemia, Lymphoblastic, Acute

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMD3100
Stem Cell Transplant
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Plerixafor, Stem cell transplantation, Stem cells, Mobilization

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Other

Arm Label

Subcutaneous (SC) Treatment Plan - Donor

Intravenous (IV) Treatment Plan - Donor

Recipients

Arm Description

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.

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.

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

Outcomes

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)
-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)
-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)
-Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir

Secondary Outcome Measures

Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)
-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)
-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)
Proportion of Donors Who Experience Infusional Toxicity (Donor Only)
-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
-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
-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

Full Information

First Posted
October 17, 2005
Last Updated
June 5, 2017
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00241358
Brief Title
Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, Leukemia, Lymphoblastic, Acute, Lymphocytic Leukemia, Chronic, Myelodysplastic Syndromes, Multiple Myeloma, Lymphoma, Non-Hodgkin, Hodgkin Disease
Keywords
Plerixafor, Stem cell transplantation, Stem cells, Mobilization

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subcutaneous (SC) Treatment Plan - Donor
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intravenous (IV) Treatment Plan - Donor
Arm Type
Experimental
Arm Description
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.
Arm Title
Recipients
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
AMD3100
Other Intervention Name(s)
Plerixafor
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Transplant
Primary Outcome Measure Information:
Title
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)
Description
-Defined as the proportion of donors collecting >2.0x106 CD34+ cells/kg [recipient weight]
Time Frame
Day 1-3
Title
Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only)
Description
-Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria
Time Frame
By Day 100 after transplant
Title
Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only)
Description
-Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir
Time Frame
Day +21
Secondary Outcome Measure Information:
Title
Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)
Description
-Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria
Time Frame
Between Day +100 and +365 post-transplant
Title
Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only)
Description
-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
Time Frame
100 days after transplant
Title
Quality of Life During Stem Cell Mobilization (Recipients Only)
Time Frame
48-72 hours after last dose of AMD3100
Title
Proportion of Donors Who Experience Infusional Toxicity (Donor Only)
Description
-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
Time Frame
Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
Title
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax
Description
-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
Time Frame
0 to 24 hours after dose of IV AMD3100
Title
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity
Description
-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
Time Frame
0 to 24 hours after dose of IV AMD3100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John F. DiPersio, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18426988
Citation
Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N, Devine H, Link DC, Calandra G, Bridger G, Westervelt P, Dipersio JF. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood. 2008 Aug 15;112(4):990-8. doi: 10.1182/blood-2007-12-130179. Epub 2008 Apr 21.
Results Reference
background
PubMed Identifier
15020611
Citation
Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, DiPersio JF. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol. 2004 Mar 15;22(6):1095-102. doi: 10.1200/JCO.2004.07.131.
Results Reference
background
PubMed Identifier
15890685
Citation
Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005 Sep 1;106(5):1867-74. doi: 10.1182/blood-2005-02-0468. Epub 2005 May 12.
Results Reference
background
PubMed Identifier
28292947
Citation
Schroeder MA, Rettig MP, Lopez S, Christ S, Fiala M, Eades W, Mir FA, Shao J, McFarland K, Trinkaus K, Shannon W, Deych E, Yu J, Vij R, Stockerl-Goldstein K, Cashen AF, Uy GL, Abboud CN, Westervelt P, DiPersio JF. Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft. Blood. 2017 May 11;129(19):2680-2692. doi: 10.1182/blood-2016-09-739722. Epub 2017 Mar 14.
Results Reference
derived
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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