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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00241358
• Collaborator: (none)
• Enrollment: 92
• Location: 1
• Arms: 3
• Duration (Months): 69.1
• Patients Per Site Per Month: 1.3

Study Details

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.

Condition or Disease	Intervention/Treatment	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

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 Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• 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
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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) [Day 1-3]

   -Defined as the proportion of donors collecting >2.0x106 CD34+ cells/kg [recipient weight]

2. Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only) [By Day 100 after transplant]

   -Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria

3. Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only) [Day +21]

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

Secondary Outcome Measures

1. Proportion of Recipients Who Experience Chronic GVHD (Recipient Only) [Between Day +100 and +365 post-transplant]

   -Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria

2. Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only) [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

3. Quality of Life During Stem Cell Mobilization (Recipients Only) [48-72 hours after last dose of AMD3100]

4. Proportion of Donors Who Experience Infusional Toxicity (Donor Only) [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

5. To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax [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

6. To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

• 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.
• 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.
• 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. Epub 2005 May 12.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00241358
• Other Study ID Numbers: 03-0349
• First Posted: Oct 18, 2005
• Last Update Posted: Jun 6, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Hematologic Neoplasms; 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; Myelodysplastic Syndromes; Plerixafor

Study Results

Participant Flow

Recruitment Details	The study was opened to participant enrollment on 05/14/2004 and closed to participant enrollment on 01/26/2009.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Period Title: Overall Study
STARTED	25	46	21
COMPLETED	25	45	20
NOT COMPLETED	0	1	1

Baseline Characteristics

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor	Total
Arm/Group 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.	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	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.	Total of all reporting groups
Overall Participants	25	46	21	92
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54	53	51	52
Sex: Female, Male (Count of Participants)
Female	5 20%	26 56.5%	8 38.1%	39 42.4%
Male	20 80%	20 43.5%	13 61.9%	53 57.6%
Region of Enrollment (participants) [Number]
United States	25 100%	46 100%	21 100%	92 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	25	0	20
Count of Participants [Participants]	22 88%	19 41.3%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	38	0
Count of Participants [Participants]	15 60%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	38	0
Count of Participants [Participants]	37 148%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 28 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, receiving non-AMD3100 mobilized cells, or death before day +100.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	28	0
Count of Participants [Participants]	10 40%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	38	0
Count of Participants [Participants]	2 8%

6. Secondary Outcome

Title	Quality of Life During Stem Cell Mobilization (Recipients Only)
Time Frame	48-72 hours after last dose of AMD3100

Outcome Measure Data

Analysis Population Description

-Quality of life questionnaires were not collected from the recipients.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	0	0

7. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	25	0	20
Count of Participants [Participants]	0 0%	0 0%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Pharmacokinetics were not performed on 2 patients who were considered replacement patients.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	0	19
Mean (Full Range) [ng/ml]	1058

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Pharmacokinetics were not performed on 2 patients who were considered replacement patients.

Arm/Group Title	Subcutaneous (SC) Treatment Plan - Donor	Recipients	Intravenous (IV) Treatment Plan - Donor
Arm/Group 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.	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	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.
Measure Participants	0	0	19
Mean (Full Range) [ng*hr/mL]	5150

Adverse Events

Arm/Group Title	Donors		Recipients
Arm/Group Description	AMD3100 SC 240 ug/kg/actual donor weight on Day 1 and possibly Day 3		Stem Cell Transplantation Day 0
All Cause Mortality
	Donors		Recipients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Donors		Recipients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/46 (4.3%)		12/46 (26.1%)
Blood and lymphatic system disorders
Iron deficiency	1/46 (2.2%)		0/46 (0%)
Cardiac disorders
Atrial fibrillation	0/46 (0%)		1/46 (2.2%)
Congestive heart failure	0/46 (0%)		1/46 (2.2%)
Tachycardia	0/46 (0%)		1/46 (2.2%)
Endocrine disorders
Adrenal insufficiency	0/46 (0%)		1/46 (2.2%)
Eye disorders
Eye pain	0/46 (0%)		1/46 (2.2%)
Gastrointestinal disorders
Abdominal pain	0/46 (0%)		2/46 (4.3%)
Diarrhea	0/46 (0%)		3/46 (6.5%)
Emesis	0/46 (0%)		1/46 (2.2%)
Heartburn/dyspepsia	0/46 (0%)		1/46 (2.2%)
Mouth pain	0/46 (0%)		1/46 (2.2%)
Mucositis	0/46 (0%)		1/46 (2.2%)
Nausea	0/46 (0%)		3/46 (6.5%)
Vomiting	0/46 (0%)		2/46 (4.3%)
General disorders
Death due to disease progression	0/46 (0%)		1/46 (2.2%)
Edema - extremities	0/46 (0%)		1/46 (2.2%)
Fever	1/46 (2.2%)		2/46 (4.3%)
Generalized weakness	0/46 (0%)		1/46 (2.2%)
Infections and infestations
C. Difficile infection	0/46 (0%)		1/46 (2.2%)
Sepsis	0/46 (0%)		1/46 (2.2%)
Investigations
Increased bilirubin	0/46 (0%)		1/46 (2.2%)
Pancytopenia	0/46 (0%)		1/46 (2.2%)
Weight loss	0/46 (0%)		2/46 (4.3%)
Metabolism and nutrition disorders
Anorexia	0/46 (0%)		2/46 (4.3%)
Hyperkalemia	0/46 (0%)		1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Ankle pain	0/46 (0%)		1/46 (2.2%)
Neck pain	1/46 (2.2%)		0/46 (0%)
Shoulder pain	1/46 (2.2%)		0/46 (0%)
Nervous system disorders
Confusion	0/46 (0%)		2/46 (4.3%)
Headache	0/46 (0%)		1/46 (2.2%)
Vasovagal reaction	1/46 (2.2%)		0/46 (0%)
Renal and urinary disorders
Increased creatinine	0/46 (0%)		1/46 (2.2%)
Renal failure	0/46 (0%)		3/46 (6.5%)
Urinary frequency	0/46 (0%)		1/46 (2.2%)
Urinary urgency	0/46 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	0/46 (0%)		1/46 (2.2%)
Dyspnea	0/46 (0%)		2/46 (4.3%)
Hypoxia	0/46 (0%)		1/46 (2.2%)
Pleural effusion	0/46 (0%)		1/46 (2.2%)
Pulmonary edema	0/46 (0%)		1/46 (2.2%)
Skin and subcutaneous tissue disorders
Erythemous rash	0/46 (0%)		1/46 (2.2%)
Rash	0/46 (0%)		1/46 (2.2%)
Vascular disorders
Hypotension	0/46 (0%)		4/46 (8.7%)
Other (Not Including Serious) Adverse Events
	Donors		Recipients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/46 (100%)		46/46 (100%)
Blood and lymphatic system disorders
Anemia	2/46 (4.3%)		0/46 (0%)
Cardiac disorders
Atrial fibrillation	0/46 (0%)		3/46 (6.5%)
Bradycardia	3/46 (6.5%)		4/46 (8.7%)
Cardiomyopathy	0/46 (0%)		1/46 (2.2%)
Congestive heart failure	0/46 (0%)		1/46 (2.2%)
Non-specific ST abnormality	1/46 (2.2%)		0/46 (0%)
Tachycardia	0/46 (0%)		5/46 (10.9%)
U wave	1/46 (2.2%)		0/46 (0%)
Vasovagal episode	2/46 (4.3%)		0/46 (0%)
Ventricular arrhythmia	0/46 (0%)		1/46 (2.2%)
Ear and labyrinth disorders
Ear pain	0/46 (0%)		1/46 (2.2%)
Otitis, middle ear	0/46 (0%)		1/46 (2.2%)
Eye disorders
Vitreous hemorrhage	0/46 (0%)		1/46 (2.2%)
Watery eye (tearing)	0/46 (0%)		2/46 (4.3%)
Gastrointestinal disorders
Colitis	0/46 (0%)		6/46 (13%)
Constipation	0/46 (0%)		4/46 (8.7%)
Cramping	3/46 (6.5%)		0/46 (0%)
Diarrhea	10/46 (21.7%)		16/46 (34.8%)
Distension/abdominal bloating	4/46 (8.7%)		2/46 (4.3%)
Dysphagia	0/46 (0%)		1/46 (2.2%)
Fistula, GI	0/46 (0%)		1/46 (2.2%)
Flatulence	8/46 (17.4%)		0/46 (0%)
Heartburn/dyspepsia	0/46 (0%)		1/46 (2.2%)
Mucositis	0/46 (0%)		18/46 (39.1%)
Nausea	9/46 (19.6%)		16/46 (34.8%)
Vomiting	0/46 (0%)		16/46 (34.8%)
General disorders
Anasarca	0/46 (0%)		3/46 (6.5%)
Chills	3/46 (6.5%)		0/46 (0%)
Cold sensation	2/46 (4.3%)		0/46 (0%)
Facial edema (head and neck)	0/46 (0%)		1/46 (2.2%)
Fatigue	4/46 (8.7%)		17/46 (37%)
Fever	0/46 (0%)		6/46 (13%)
Generalized weakness	0/46 (0%)		4/46 (8.7%)
Hypothermia	0/46 (0%)		1/46 (2.2%)
Injection site reaction	9/46 (19.6%)		0/46 (0%)
Lower extremities edema	0/46 (0%)		4/46 (8.7%)
Sweating (diaphoresis)	5/46 (10.9%)		0/46 (0%)
Warm sensation	5/46 (10.9%)		0/46 (0%)
Hepatobiliary disorders
Cholestasis	0/46 (0%)		1/46 (2.2%)
Infections and infestations
Bacteremia	0/46 (0%)		3/46 (6.5%)
Febrile neutropenia	0/46 (0%)		19/46 (41.3%)
Foliculitis	1/46 (2.2%)		3/46 (6.5%)
G-tube site infection	0/46 (0%)		1/46 (2.2%)
Interstitial pneumonia	0/46 (0%)		1/46 (2.2%)
Sinusitis	1/46 (2.2%)		0/46 (0%)
Upper respiratory infection	0/46 (0%)		2/46 (4.3%)
Urinary tract infection	0/46 (0%)		4/46 (8.7%)
Viremia	0/46 (0%)		3/46 (6.5%)
Investigations
Hyperbilirubinemia	0/46 (0%)		3/46 (6.5%)
Metabolism and nutrition disorders
Anorexia	0/46 (0%)		7/46 (15.2%)
Hypercalcemia	0/46 (0%)		1/46 (2.2%)
Hyperglycemia	0/46 (0%)		5/46 (10.9%)
Hyperkalemia	0/46 (0%)		2/46 (4.3%)
Hypermagnesemia	0/46 (0%)		1/46 (2.2%)
Hypernatremia	0/46 (0%)		1/46 (2.2%)
Hyperphosphatemia	0/46 (0%)		1/46 (2.2%)
Hyperuricemia	0/46 (0%)		1/46 (2.2%)
Hypocalcemia	0/46 (0%)		1/46 (2.2%)
Hypokalemia	0/46 (0%)		1/46 (2.2%)
Hypomagnesemia	0/46 (0%)		1/46 (2.2%)
Hyponatremia	0/46 (0%)		2/46 (4.3%)
Musculoskeletal and connective tissue disorders
Ankle pain	0/46 (0%)		1/46 (2.2%)
Arm pain	0/46 (0%)		1/46 (2.2%)
Back pain	2/46 (4.3%)		4/46 (8.7%)
Bone pain	0/46 (0%)		2/46 (4.3%)
Extremity walking (gait/walking)	0/46 (0%)		3/46 (6.5%)
Hip pain	1/46 (2.2%)		1/46 (2.2%)
Joint pain	1/46 (2.2%)		0/46 (0%)
Knee pain	0/46 (0%)		1/46 (2.2%)
Leg pain	0/46 (0%)		2/46 (4.3%)
Muscle weakness	0/46 (0%)		1/46 (2.2%)
Neck pain	1/46 (2.2%)		0/46 (0%)
Shoulder blade pain	4/46 (8.7%)		0/46 (0%)
Shoulder pain	0/46 (0%)		1/46 (2.2%)
Spine pain	0/46 (0%)		1/46 (2.2%)
Nervous system disorders
Dizziness	0/46 (0%)		2/46 (4.3%)
Extrapyramidal involuntary movement	2/46 (4.3%)		3/46 (6.5%)
Feet tremor	0/46 (0%)		1/46 (2.2%)
Hand tremor	0/46 (0%)		6/46 (13%)
Headache	2/46 (4.3%)		7/46 (15.2%)
Lightheadedness	13/46 (28.3%)		0/46 (0%)
Seizure	0/46 (0%)		3/46 (6.5%)
Sensory neuropathy	15/46 (32.6%)		3/46 (6.5%)
Spine pain	1/46 (2.2%)		0/46 (0%)
Psychiatric disorders
Confusion	0/46 (0%)		2/46 (4.3%)
Insomnia	1/46 (2.2%)		2/46 (4.3%)
Mental status change	0/46 (0%)		2/46 (4.3%)
Mood alteration	1/46 (2.2%)		5/46 (10.9%)
Renal and urinary disorders
Bladder spasm	0/46 (0%)		1/46 (2.2%)
Incontinence	0/46 (0%)		2/46 (4.3%)
Renal failure	0/46 (0%)		3/46 (6.5%)
Urinary color change	0/46 (0%)		1/46 (2.2%)
Urinary frequency/urgency	0/46 (0%)		3/46 (6.5%)
Reproductive system and breast disorders
Testicular pain	0/46 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm wheezing	0/46 (0%)		1/46 (2.2%)
Cough	0/46 (0%)		7/46 (15.2%)
Dyspnea	0/46 (0%)		2/46 (4.3%)
Edema/larynx	0/46 (0%)		1/46 (2.2%)
Hemoptisis	0/46 (0%)		1/46 (2.2%)
Paranasal reactions	0/46 (0%)		3/46 (6.5%)
Pleural effusion	0/46 (0%)		3/46 (6.5%)
Respiratory distress	0/46 (0%)		3/46 (6.5%)
Tachypnea	0/46 (0%)		3/46 (6.5%)
Throat pain	0/46 (0%)		1/46 (2.2%)
Skin and subcutaneous tissue disorders
Alopecia	1/46 (2.2%)		4/46 (8.7%)
Bruising	1/46 (2.2%)		1/46 (2.2%)
Decubitus ulcer	0/46 (0%)		1/46 (2.2%)
Dry skin	0/46 (0%)		1/46 (2.2%)
Petequiae	0/46 (0%)		1/46 (2.2%)
Pruritus/itching	1/46 (2.2%)		1/46 (2.2%)
Rash/desquamation	0/46 (0%)		14/46 (30.4%)
Ulceration	0/46 (0%)		2/46 (4.3%)
Vascular disorders
Hypertension	2/46 (4.3%)		2/46 (4.3%)
Hypotension	3/46 (6.5%)		0/46 (0%)
Thrombosis/embolism (DVT)	2/46 (4.3%)		3/46 (6.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.