Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant

• Sponsor: Mitchell Horwitz, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01280955
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 41
• Locations: 2
• Arm: 1
• Actual Duration (Months): 41
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This phase I/II clinical trial will test the safety and the efficacy of post transplant administration of plerixafor in enhancing hematological recovery in humans. Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The investigators plan to enroll a total of 50 patients for this study (30 patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with umbilical cord blood transplant). During phase I study, a small number of patients (3-6 patients from each group) will be enrolled to determine the safety of post transplant administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment. Limiting toxicities are defined as primary or secondary graft failure, plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are met from the investigators phase I study, the investigators will proceed with phase II study to determine the efficacy of post transplant administration of plerixafor in enhancing haematological recovery. The experimental aspect of this study is the use of plerixafor and all other aspects of care will be in line with the standard of care. Both Phase I and Phase II patients will be combined for efficacy analysis, and data collected from this study will be compared with the investigators historical control. The results from this study will set the stage and provide the justification for a larger phase 3 trial.

Condition or Disease	Intervention/Treatment	Phase
Failure of Bone Marrow Graft	Drug: Plerixafor	Phase 1/Phase 2

Detailed Description

Recruitment to this trial will be stratified by donor type as HLA (human leukocyte antigen) matched sibling, matched unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell count of of 1.5 X 10(7)/kg. Post-transplant GVHD (graft versus host disease) prophylaxis will be given per institutional standard.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation
• Actual Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transplant Recipients Transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.	Drug: Plerixafor; Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.; Other Names: AMD3100 Mozobil

Outcome Measures

Primary Outcome Measures

1. Time to Neutrophil Recovery [100 Days post Transplant]

   leukocytes > 500/ul on 2 consecutive days

2. Time to Platelet Recovery [100 Days Post Transplant]

   platelet > 20,000/ul on 2 consecutive days

3. Plerixafor-associated Adverse Events [100 Days Post Transplant]

Secondary Outcome Measures

1. Transplant-related Mortality [100 Days Post Transplant]

2. Absolute Lymphocyte Count at Day 90 [90 days]

   Cell reconstitution - absolute lymphocyte count at day 90 post transplant.

3. IL-12 at Day 30 [30 days]

   IL-12 at day 30; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

4. Participants Experiencing Grade II-IV Acute Graft Versus Host Disease [100 days]

   We are reporting on the number of participants experiencing a grade II-IV acute graft versus host disease will be assessed weekly through Day 100 post transplant. Staging and grading of Acute GvHD is graded by pattern of organ involvement and clinical performance status using the Grading Index of Acute GvHD (Gluckman) and the Grading Index of Acute GVHD by the CIBMTR (Centers for International Blood and Marrow Transplant Research)

5. CD3+ Cell Count at Day 90 [90 Days]

   Cell reconstitution - CD3+ cell count at day 90 post transplant. This is a marker for the function of your immune system.

6. CD4 Cell Count at Day 90 [90 days]

   CD4 cell count at Day 90; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

7. CD8 Cell Count at Day 90 [90 days]

   CD8 cell count at Day 90; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

8. NK Cell Count at Day 90 [90 days]

   NK cell count at Day 90;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

9. B Cell Count at Day 90 [90 days]

   B cell count at Day 90; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

10. IFN Gamma at Day 30 [30 days]

    IFN gamma at day 30; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

11. TNF-alpha at Day 30 [30 days]

    TNF-alpha at day 30; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.

12. CD4 Cell Count at Day 30 [30 days]

    CD4 cell count at Day 30; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

13. CD4 Cell Count at Day 60 [60 days]

    CD4 cell count at Day 60; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

14. CD8 Cell Count at Day 30 [30 days]

    CD8 cell count at Day 30; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

15. CD8 Cell Count at Day 60 [60 days]

    CD8 cell count at Day 60; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

16. NK Cell Count at Day 30 [30 days]

    NK cell count at Day 30;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

17. NK Cell Count at Day 60 [60 days]

    NK cell count at Day 60;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

18. B Cell Count at Day 30 [30 days]

    B cell count at Day 30; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

19. B Cell Count at Day 60 [60 days]

    B cell count at Day 60; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

20. IL-12 at Day 7 [7 days]

    IL-12 at day 7; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

21. IL-12 at Day 14 [14 days]

    IL-12 at day 14; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

22. IFN Gamma at Day 7 [7 days]

    IFN gamma at day 7; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

23. IFN Gamma at Day 14 [14 days]

    IFN gamma at day 14; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

24. TNF-alpha at Day 7 [7 days]

    TNF-alpha at day 7; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.

25. TNF-alpha at Day 14 [14 days]

    TNF-alpha at day 14; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18 to 65 years.

• 8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DR Beta1)matched unrelated donor or 4/6 or better HLA matched cord blood.

• Patients with high risk hematologic malignancies who are appropriate candidates for a myeloablative allogeneic stem cell transplantation.

• Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.

• ECOG performance status < or equal to 2

• Patients must have adequate function of other organ systems as measured by:

• Creatinine clearance (by Cockcroft Gault equation) > or equal to 30ml/min. Hepatic transaminases (ALT/AST) < or equal to 4 x normal, bilirubin < or equal to 2.0 mg/dl.

• Pulmonary function tests demonstrating FVC and FEV1 of > or equal to 50% of predicted for age and DLCO > or equal to 50% of predicted.

• Ejection fraction of > or equal to 45% by echocardiogram, radionuclide scan or cardiac MRI.

• Patients must be HIV negative.

• Patients must not be pregnant.

Exclusion Criteria:

• Patients with > 5% blasts in bone marrow or peripheral circulation.

• Uncontrolled infection.

• Class III or IV angina as per NYHA criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27705
2	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Mitchell Horwitz, MD
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Mitchell Horwitz, MD, Duke University
• Principal Investigator: Saurabh Chhabra, MD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitchell Horwitz, MD, Assoc Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT01280955
• Other Study ID Numbers: Pro00024433
• First Posted: Jan 21, 2011
• Last Update Posted: Apr 25, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Mitchell Horwitz, MD, Assoc Professor of Medicine, Duke University: Plerixafor and Allogeneic Myeloablative Stem Cell Transplant
• Additional relevant MeSH terms: Plerixafor

Study Results

Participant Flow

Recruitment Details	Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The first subject was consented on 9/28/2011. The study closed to accrual on 5/27/2014.
Pre-assignment Detail	41 participants signed consent and 30 received transplant. 11 patients who signed consent were screen failures. Reasons patients did not receive transplant included lack of donor, insurance denial, too much disease, uncontrolled infection, class III or IV angina. 29 participants were used in results analysis because one participant withdrew.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Period Title: Overall Study
STARTED	30
COMPLETED	27
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	14 48.3%
Male	15 51.7%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Time to Neutrophil Recovery
Description	leukocytes > 500/ul on 2 consecutive days
Time Frame	100 Days post Transplant

Outcome Measure Data

Analysis Population Description

Out of the 30 transplant recipients, one participant withdrew and was therefore not analyzed

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	29
Median (95% Confidence Interval) [days]	17

2. Primary Outcome

Title	Time to Platelet Recovery
Description	platelet > 20,000/ul on 2 consecutive days
Time Frame	100 Days Post Transplant

Outcome Measure Data

Analysis Population Description

Out of the 30 transplant recipients, one participant withdrew and was therefore not analyzed

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	29
Median (95% Confidence Interval) [days]	18

3. Primary Outcome

Title	Plerixafor-associated Adverse Events
Time Frame	100 Days Post Transplant

Outcome Measure Data

Analysis Population Description

Out of the 30 transplant recipients, one participant withdrew and was therefore not analyzed

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	29
GI upset	1
nausea	1
diarrhea	2
fatigue	1
rash	1
pneumonia	3
bruising	1

4. Secondary Outcome

Title	Transplant-related Mortality
Time Frame	100 Days Post Transplant

Outcome Measure Data

Analysis Population Description

Out of the 30 transplant recipients, one participant withdrew and was therefore not analyzed

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	29
Number [participants]	11 37.9%

5. Secondary Outcome

Title	Absolute Lymphocyte Count at Day 90
Description	Cell reconstitution - absolute lymphocyte count at day 90 post transplant.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

the population includes all participants for which we have data at day 90

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of lymphocytes]	549

6. Secondary Outcome

Title	IL-12 at Day 30
Description	IL-12 at day 30; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes all participants for which we have data at day 30

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	26
Median (Full Range) [pg/mL]	40.7

7. Secondary Outcome

Title	Participants Experiencing Grade II-IV Acute Graft Versus Host Disease
Description	We are reporting on the number of participants experiencing a grade II-IV acute graft versus host disease will be assessed weekly through Day 100 post transplant. Staging and grading of Acute GvHD is graded by pattern of organ involvement and clinical performance status using the Grading Index of Acute GvHD (Gluckman) and the Grading Index of Acute GVHD by the CIBMTR (Centers for International Blood and Marrow Transplant Research)
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	29
Grade 2	5 17.2%
Grade 3	5 17.2%

8. Secondary Outcome

Title	CD3+ Cell Count at Day 90
Description	Cell reconstitution - CD3+ cell count at day 90 post transplant. This is a marker for the function of your immune system.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

the population includes all participants for which we have data at day 90

Arm/Group Title	Transplant Recipients
Arm/Group Description	Transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs. Plerixafor: Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of CD3+ cells]	655

9. Secondary Outcome

Title	CD4 Cell Count at Day 90
Description	CD4 cell count at Day 90; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

The population includes subjects for which we have data at day 90.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of CD4 cells]	180

10. Secondary Outcome

Title	CD8 Cell Count at Day 90
Description	CD8 cell count at Day 90; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at day 90

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of CD8 cells]	172

11. Secondary Outcome

Title	NK Cell Count at Day 90
Description	NK cell count at Day 90;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 90.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of NK cells]	137

12. Secondary Outcome

Title	B Cell Count at Day 90
Description	B cell count at Day 90; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 90.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	11
Median (Full Range) [number of B cells]	7

13. Secondary Outcome

Title	IFN Gamma at Day 30
Description	IFN gamma at day 30; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	26
Median (Full Range) [pg/mL]	8.6

14. Secondary Outcome

Title	TNF-alpha at Day 30
Description	TNF-alpha at day 30; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	26
Median (Full Range) [pg/mL]	146.5

15. Secondary Outcome

Title	CD4 Cell Count at Day 30
Description	CD4 cell count at Day 30; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

The population includes subjects for which we have data at day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	13
Median (Full Range) [number of CD4 cells]	252

16. Secondary Outcome

Title	CD4 Cell Count at Day 60
Description	CD4 cell count at Day 60; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

The population includes subjects for which we have data at day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	6
Median (Full Range) [number of CD4 cells]	220

17. Secondary Outcome

Title	CD8 Cell Count at Day 30
Description	CD8 cell count at Day 30; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at day 30

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	13
Median (Full Range) [number of CD8 cells]	255

18. Secondary Outcome

Title	CD8 Cell Count at Day 60
Description	CD8 cell count at Day 60; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at day 60

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	6
Median (Full Range) [number of CD8 cells]	199

19. Secondary Outcome

Title	NK Cell Count at Day 30
Description	NK cell count at Day 30;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	13
Median (Full Range) [number of NK cells]	226

20. Secondary Outcome

Title	NK Cell Count at Day 60
Description	NK cell count at Day 60;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 60.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	6
Median (Full Range) [number of NK cells]	221

21. Secondary Outcome

Title	B Cell Count at Day 30
Description	B cell count at Day 30; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 30.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	13
Median (Full Range) [number of B cells]	6

22. Secondary Outcome

Title	B Cell Count at Day 60
Description	B cell count at Day 60; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

the population includes subjects for which we have data at Day 60.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	6
Median (Full Range) [number of B cells]	18

23. Secondary Outcome

Title	IL-12 at Day 7
Description	IL-12 at day 7; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

the population includes all participants for which we have data at day 7

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	28
Median (Full Range) [pg/mL]	8.4

24. Secondary Outcome

Title	IL-12 at Day 14
Description	IL-12 at day 14; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

the population includes all participants for which we have data at day 14

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	27
Median (Full Range) [pg/mL]	13.3

25. Secondary Outcome

Title	IFN Gamma at Day 7
Description	IFN gamma at day 7; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 7.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	28
Median (Full Range) [pg/mL]	3.9

26. Secondary Outcome

Title	IFN Gamma at Day 14
Description	IFN gamma at day 14; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 14.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	27
Median (Full Range) [pg/mL]	20.0

27. Secondary Outcome

Title	TNF-alpha at Day 7
Description	TNF-alpha at day 7; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 7.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	28
Median (Full Range) [pg/mL]	15.9

28. Secondary Outcome

Title	TNF-alpha at Day 14
Description	TNF-alpha at day 14; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

the population includes subject for which we have data at Day 14.

Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Measure Participants	27
Median (Full Range) [pg/mL]	43.8

Adverse Events

Time Frame	adverse events are collected for 1 year post transplant
Adverse Event Reporting Description	Adverse Events were monitored for 29 transplant recipients
Arm/Group Title	Transplant Recipients
Arm/Group Description	This arm includes transplant recipients from matched sibling donors and dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs. Adverse Events were monitored for 29 transplant recipients
All Cause Mortality
	Transplant Recipients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Transplant Recipients
	Affected / at Risk (%)	# Events
Total	12/29 (41.4%)
General disorders
death	4/29 (13.8%)	4
death	3/29 (10.3%)	3
death	2/29 (6.9%)	2
Infections and infestations
encephalitis	1/29 (3.4%)	1
pneumonia	1/29 (3.4%)	1
small bowel (NOS)	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Transplant Recipients
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Blood and lymphatic system disorders
engraftment syndrome	2/29 (6.9%)	2
anemia	1/29 (3.4%)	1
pancytopenia	1/29 (3.4%)	1
neutropenia	1/29 (3.4%)	1
relapsed disease	1/29 (3.4%)	1
Edema	13/29 (44.8%)	18
Hemoglobin	1/29 (3.4%)	1
Hemorrhage, pulmonary / upper respiratory	2/29 (6.9%)	2
Leukocytes (total WBC)	1/29 (3.4%)	1
Neutrophils / granulocytes (ANC / AGC)	1/29 (3.4%)	1
platelets	3/29 (10.3%)	3
Thrombotic microangiopathy	1/29 (3.4%)	1
Cardiac disorders
tacycardia	7/29 (24.1%)	9
Hypertension	1/29 (3.4%)	1
Hypotension	5/29 (17.2%)	5
Pain - Chest / thorax NOS	1/29 (3.4%)	1
Sinus Tachycardia	8/29 (27.6%)	10
Ear and labyrinth disorders
Hearing Loss	1/29 (3.4%)	1
Otitis, middle ear (non-infectious)	1/29 (3.4%)	1
Endocrine disorders
Adrenal insufficiency	1/29 (3.4%)	1
Thyroid function, low (hypothyroidism)	1/29 (3.4%)	1
Eye disorders
keratoconjunctivitis (Dry Eye Syndrome)	2/29 (6.9%)	2
subconjunctivial hemorrhage	1/29 (3.4%)	2
rheum (crusty eye)	2/29 (6.9%)	4
Vision - blurred vision	1/29 (3.4%)	1
photophobia	1/29 (3.4%)	1
Watery eye (epiphora, tearing)	1/29 (3.4%)	1
Gastrointestinal disorders
Anorexia	5/29 (17.2%)	7
Constipation	4/29 (13.8%)	4
Dehydration	3/29 (10.3%)	3
Diarrhea	16/29 (55.2%)	24
odynophagia	1/29 (3.4%)	1
oropharyngeal erythema	7/29 (24.1%)	13
Heartburn / dyspepsia	3/29 (10.3%)	4
Hemorrhoids	1/29 (3.4%)	1
Mucositis / Stomatitis (clinical exam)	28/29 (96.6%)	34
Pain - Abdomen NOS	8/29 (27.6%)	10
Vomiting	10/29 (34.5%)	26
General disorders
pyrexia (fever)	6/29 (20.7%)	6
fatigue	1/29 (3.4%)	1
frail appearance	1/29 (3.4%)	2
hyperthermia (overheating)	1/29 (3.4%)	1
Dental: caries	1/29 (3.4%)	1
Dry mouth / salivary gland (xerostomia)	1/29 (3.4%)	1
Fatigue (asthenia, lethargy, malaise)	9/29 (31%)	11
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	5/29 (17.2%)	7
pain - general body ache	2/29 (6.9%)	2
Insomnia	5/29 (17.2%)	5
Rigors / chills	2/29 (6.9%)	3
Weight gain	1/29 (3.4%)	1
Hepatobiliary disorders
hyperbilirubinemia	1/29 (3.4%)	1
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3/29 (10.3%)	4
hypogammagloulinemia	1/29 (3.4%)	1
Infections and infestations
Febrile neutropenia	17/29 (58.6%)	19
Febrile neutropenia	6/29 (20.7%)	8
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	9/29 (31%)	10
viremia	10/29 (34.5%)	13
rsv pneumonia	4/29 (13.8%)	4
Infection with unknown ANC - Blood	2/29 (6.9%)	2
Infection with unknown ANC - Lung (pneumonia)	1/29 (3.4%)	1
Infection with unknown ANC - Sinus	2/29 (6.9%)	3
Infection with unknown ANC - Skin (cellulitis)	2/29 (6.9%)	3
Infection with unknown ANC - Urinary tract NOS	1/29 (3.4%)	1
Infection without febrile neutropenia	1/29 (3.4%)	3
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	1/29 (3.4%)	1
ALT, SGPT (serum glutamic pyruvic transaminase)	2/29 (6.9%)	2
AST, SGOT (serum glutamic oxaloacetic transaminase)	2/29 (6.9%)	2
Bilirubin (hyperbilirubinemia)	2/29 (6.9%)	2
Creatinine	2/29 (6.9%)	2
Glucose, serum-high (hyperglycemia)	1/29 (3.4%)	1
Magnesium, serum-low (hypomagnesemia)	6/29 (20.7%)	6
Phosphate, serum-low (hypophosphatemia)	1/29 (3.4%)	1
Taste Alteration (dysgeusia)	3/29 (10.3%)	3
Musculoskeletal and connective tissue disorders
Extremity-lower (gait / walking)	1/29 (3.4%)	1
Fracture	2/29 (6.9%)	2
Muscle weakness, generalized or specific area (not due to neuropathy)	4/29 (13.8%)	5
asthenia	6/29 (20.7%)	10
Musculoskeletal / Soft Tissue injury	4/29 (13.8%)	6
Pain - Back	4/29 (13.8%)	5
Pain - Bone	1/29 (3.4%)	1
Pain - Extremity-limb	2/29 (6.9%)	4
Pain - Joint	2/29 (6.9%)	2
Pain- groin	5/29 (17.2%)	8
Potassium, serum-low (hypokalemia)	3/29 (10.3%)	6
Nervous system disorders
presbyacusis (Hearing loss)	2/29 (6.9%)	2
Confusion	1/29 (3.4%)	1
Dizziness	3/29 (10.3%)	3
Mental status decrease	3/29 (10.3%)	3
Mood Alteration - Anxiety	4/29 (13.8%)	4
pain - headache	3/29 (10.3%)	3
Neurology	1/29 (3.4%)	3
fall	1/29 (3.4%)	1
lethargy	1/29 (3.4%)	1
peripheral neuropathy	2/29 (6.9%)	2
Pain - Head / headache	6/29 (20.7%)	9
Tremor	3/29 (10.3%)	3
Renal and urinary disorders
Bladder spasms	1/29 (3.4%)	1
hematuria	8/29 (27.6%)	14
polyuria (Urinary frequency / urgency)	2/29 (6.9%)	2
Reproductive system and breast disorders
Pain - Ovulatory	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/29 (13.8%)	4
Dyspnea (shortness of breath)	4/29 (13.8%)	5
Hiccoughs (hiccups, singultus)	1/29 (3.4%)	1
Hypoxia	2/29 (6.9%)	3
Nasal cavity / paranasal sinus reactions	2/29 (6.9%)	2
Nausea	15/29 (51.7%)	25
Pain - Throat / pharynx / larynx	2/29 (6.9%)	2
Pleural effusion (non-malignant)	1/29 (3.4%)	2
Pneumonitis / pulmonary infiltrates	3/29 (10.3%)	3
Pulmonary / Upper Respiratory infiltrates	10/29 (34.5%)	12
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	4/29 (13.8%)	4
contact dermatitis	1/29 (3.4%)	1
groin irratation	1/29 (3.4%)	1
pallor	1/29 (3.4%)	2
erythema	1/29 (3.4%)	2
scratch marks	1/29 (3.4%)	2
purpuric lesion	1/29 (3.4%)	1
perianal lesion	1/29 (3.4%)	1
xeroderma (Dry Skin)	4/29 (13.8%)	4
Hair Loss / Alopecia (scalp or body)	4/29 (13.8%)	4
Hyperpigmentation	3/29 (10.3%)	5
Pruritus / itching	2/29 (6.9%)	4
Rash / desquamation	13/29 (44.8%)	19
Rash: acne / acneiform	1/29 (3.4%)	1
Vascular disorders
Thrombosis / embolism (vascular access-related)	3/29 (10.3%)	3

Limitations/Caveats

Study was limited to recipients of matched adult donor grafts

More Information

Certain Agreements

Principal Investigators are NOT 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.