Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01158118
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 2
• Actual Duration (Months): 69
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). These stem cells will be collected from the donor and transplanted into their sibling. The investigators believe that the two drugs together will provide enough stem cells for transplantation and may also reduce the risk of graft versus host disease.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma	Drug: Sargramostim; Drug: Plerixafor	Phase 2

Detailed Description

The main purpose of this study is to gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). Stem cells can be taken from the bone marrow of the pelvic bones or from the blood following treatment with drugs called growth factors; sargramostim is such a drug. Once stem cells leave the bone marrow and circulate in the blood, they are called peripheral blood stem cells (PBSCs). These cells can be collected through a routine procedure called apheresis, which involves placing two IVs into the arm which are connected to an apheresis machine; the machine then takes blood from the body, removes the stem cells, and returns the blood to the body.

Normally, a growth factor called filgrastim is given to donors in order to collect the stem cells used for transplantation. However, when stem cells collected using filgrastim are transplanted in patients, a possible unpredictable complication is graft versus host disease. It's thought that using a different growth factor such as sargramostim might reduce the occurrences of graft versus host disease in patients. However, sargramostim alone does not provide as many stem cells for transplantation as other growth factors. Plerixafor is another drug that can increase the number of PBSCs in a donor, but like with sargramostim, plerixafor alone does not always provide enough stem cells. This is why sargramostim and plerixafor are being combined in this study: the investigators believe that the two drugs together will provide enough stem cells for transplantation and may also reduce the risk of graft versus host disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial Evaluating the Safety and Efficacy of Plerixafor and Sargramostim (GM-CSF) for the Mobilization of Peripheral Blood Stem Cells (PBSC) From Normal, HLA-Matched Allogeneic Sibling Donors
• Actual Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Jan 15, 2014
• Actual Study Completion Date: Dec 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 - Donor Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.	Drug: Sargramostim; Other Names: GM-CSF, Leukine ; Drug: Plerixafor; Other Names: AMD3100, Mozobil
No Intervention: Arm 2 - Recipient Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day

Outcome Measures

Primary Outcome Measures

1. Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation [Up to 6 days]

   The primary endpoint is to reduce the number of donors treated with GM-CSF who require a second collection to obtain a minimum CD34/Kg (2 x 106) necessary for allogeneic stem cell transplantation when compared to historic controls mobilized with GM-CSF or plerixafor alone. A reduction in failed first leukapheresis from 40% to less than 10% as seen with G-CSF alone would be considered clinically meaningful.

Secondary Outcome Measures

1. Proportion of Donors Who Experience Grade 3-4 Infusion Toxicity [30 days after completion of therapy (estimated to be 36 days)]

   Infusional toxicity will be evaluated by measuring the patient's blood pressure, heart rate, respirations and temperature one hour prior to the allograft infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours, and 6 hours post infusion. Donors will have vital signs collected at each time point. EKGs will be performed immediately prior to IV AMD3100 and one hour after infusion.

2. Number of Donors Who Mobilize ≥ 2x10^6 CD34+ Cells/Kg Recipient Weight Safely Following One or Two Aphereses [Up to 6 days]

   -The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. If it contains at least 2x10^6 CD34+ cells/kg, then the procedure will be considered successful.

3. Percentage of Donors Who Reach 5x10^6 CD34+ Cells/Kg Recipient Weight in 1 or 2 Aphereses [6 days]

   -The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. The percentage of donors who reach at least 5x10^6 CD34+ cells/Kg recipient weight will be analyzed for this outcome measure.

4. Determine if Peripheral Blood Stem Cell Products Collected After Mobilization With IV Plerixafor Can be Used Safely for Hematopoietic Cell Transplantation in HLA-matched Recipients as Measured by Time to Neutrophil Engraftment (Recipient Only) [Up to Day 21]

   -Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.

5. Kinetics of Immune Reconstitution as Measured by Time to Neutrophil Engraftment (Recipient Only) [Up to Day 100]

   -Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.

6. Kinetics of Immune Reconstitution as Measured by Time to Platelet Engraftment (Recipient Only) [Up to Day 180]

   -Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 7 days.

7. Rate of Acute Graft vs. Host Disease (GvHD) (Recipient Only) [Up through Day 100]

   -Incidence and severity of acute GVHD will be assessed based on the Seattle criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).

8. Rate of Chronic Graft vs. Host Disease (GvHD) (Recipient Only) [Day 100-1 year]

   Incidence and severity of chronic GVHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).

9. Transplant Related Mortality (Recipient Only) [100 days]

   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.

10. Relapse and Disease Progression Rate [Up to 1 year]

    -A patient will be considered relapsed (disease progressed) when there is a recurrence of the original malignant disease after transplantation.

11. Death of Any Cause (Recipients Only) [Up to 1 year]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Donor Eligibility

• Donor is 18 to 65 years of age inclusive.

• If female and of child-bearing age, donor must be non-pregnant, not breastfeeding, and agree to use adequate contraception.

• Donor is a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

• Donor has adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.

• Donor has adequate renal function as defined by a calculated serum creatinine clearance of ≥56 ml/min for females and ≥64 ml/min for males.

• Donor has adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis.

• Donor has 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.

• Donor must be HIV-1&2 antibody and HTLV-I&II antibody sero-negative, by FDA licensed test.

• Donor must have an ECOG performance status of 0 or 1.

• Donor must demonstrate ability to be compliant with study regimen.

• Donor must not have an active infection at the time of study entry.

• Donor does not have active alcohol or substance abuse within 6 months of study entry.

• Donor is not currently enrolled on another investigational agent study.

• Donor does not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation.

• Ability of the donor to understand and the willingness to sign a written informed consent document.

Recipient Eligibility

• Recipient must have available the successful collection of a GM-CSF + plerixafor mobilized product. When an adequate collection cannot be obtained, G-CSF will be used and some recipients may need to receive a combined product of mobilized cells with plerixafor + GM-CSF and G-CSF mobilized cells. Recipients who receive less than 2.0 X 106 CD34+ cells/kg/actual recipient weight after six days of GM-CSF and two days of IV plerixafor will not be considered "eligible" but followed per protocol for safety purposes only.

• Recipient is 18 to 65 years of age inclusive.

• Recipient is willing and has a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

• Recipient must provide signed informed consent.

• If female and of child-bearing age, recipient must be non-pregnant, not breastfeeding, and using adequate contraception.

• Recipient must have one of the following diagnoses:

• Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse,

• Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse,

• Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System,

• Chronic myelogenous leukemia (CML) in accelerated or second chronic phase,

• Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse,

• Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens, OR

• Multiple myeloma (MM), Stage 2-3.

• Myeloproliferative disorder or neoplasm

• Recipient must have adequate cardiac function with a left ventricular ejection fraction ≥ 40%.

• Recipient must have adequate pulmonary function defined as NO severe or symptomatic restrictive or obstructive lung disease, and formal pulmonary function testing showing an FEV1 ≥50% of predicted and a DLCO ≥40% of predicted, corrected for hemoglobin.

• Recipient must have adequate renal function as defined by a serum creatinine clearance (Cockcroft-Gault equation)of ≥56 ml/min for females and ≥64 ml/min for males of normal

• Recipient must have adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis.

• Recipient must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous CNS 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.

• Recipient must have no evidence of active infection at the time of the transplant preparative regimen or at time of transplantation.

• Recipient must be HIV-1&2 antibody and HTLV-I & II antibody sero-negative, by FDA licensed test.

• Recipient has an ECOG performance status of 0 or 1.

• Recipient must demonstrate ability to be compliant with medical regimen.

• Recipient must not have active alcohol or substance abuse within 6 months of study entry.

• Recipient must not be enrolled on another investigational agent concurrently.

• Recipient must not have any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient.

• Recipient must have a life expectancy of greater than 4 weeks.

• Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

Donor Exclusion Criteria in addition to that stated above

• Donor may not be receiving any other investigational agents.

• Donor may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to plerixafor or GM-CSF, or known hypersensitivity to yeast-derived products or any component of the product.

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: Mark Schroeder, M.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

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01158118
• Other Study ID Numbers: 10-1154 / 201108083
• First Posted: Jul 8, 2010
• Last Update Posted: Jun 5, 2017
• Last Verified: May 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: Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Additional relevant MeSH terms: Leukemia; Multiple Myeloma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Plerixafor; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Arm 1 - Donor	Arm 2 - Recipient
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Period Title: Overall Study
STARTED	24	24
COMPLETED	23	21
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Arm 1 - Donor	Arm 2 - Recipient	Total
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day	Total of all reporting groups
Overall Participants	24	24	48
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53	57	56
Sex: Female, Male (Count of Participants)
Female	13 54.2%	8 33.3%	21 43.8%
Male	11 45.8%	16 66.7%	27 56.3%
Region of Enrollment (participants) [Number]
United States	24 100%	23 95.8%	48 100%

Outcome Measures

1. Primary Outcome

Title	Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation
Description	The primary endpoint is to reduce the number of donors treated with GM-CSF who require a second collection to obtain a minimum CD34/Kg (2 x 106) necessary for allogeneic stem cell transplantation when compared to historic controls mobilized with GM-CSF or plerixafor alone. A reduction in failed first leukapheresis from 40% to less than 10% as seen with G-CSF alone would be considered clinically meaningful.
Time Frame	Up to 6 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Donor
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.
Measure Participants	23
Count of Participants [Participants]	4 16.7%

2. Secondary Outcome

Title	Proportion of Donors Who Experience Grade 3-4 Infusion Toxicity
Description	Infusional toxicity will be evaluated by measuring the patient's blood pressure, heart rate, respirations and temperature one hour prior to the allograft infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours, and 6 hours post infusion. Donors will have vital signs collected at each time point. EKGs will be performed immediately prior to IV AMD3100 and one hour after infusion.
Time Frame	30 days after completion of therapy (estimated to be 36 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Donor
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.
Measure Participants	23
Count of Participants [Participants]	2 8.3%

3. Secondary Outcome

Title	Number of Donors Who Mobilize ≥ 2x10^6 CD34+ Cells/Kg Recipient Weight Safely Following One or Two Aphereses
Description	-The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. If it contains at least 2x10^6 CD34+ cells/kg, then the procedure will be considered successful.
Time Frame	Up to 6 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Donor
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.
Measure Participants	23
Count of Participants [Participants]	23 95.8%

4. Secondary Outcome

Title	Percentage of Donors Who Reach 5x10^6 CD34+ Cells/Kg Recipient Weight in 1 or 2 Aphereses
Description	-The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. The percentage of donors who reach at least 5x10^6 CD34+ cells/Kg recipient weight will be analyzed for this outcome measure.
Time Frame	6 days

Outcome Measure Data

Analysis Population Description

-If patients achieved ≥ 2x10^6 CD34+ cells/Kg, they were not required to go on to a second day of collection

Arm/Group Title	Arm 1 - Donor
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.
Measure Participants	23
Count of Participants [Participants]	8 33.3%

5. Secondary Outcome

Title	Determine if Peripheral Blood Stem Cell Products Collected After Mobilization With IV Plerixafor Can be Used Safely for Hematopoietic Cell Transplantation in HLA-matched Recipients as Measured by Time to Neutrophil Engraftment (Recipient Only)
Description	-Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.
Time Frame	Up to Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Count of Participants [Participants]	20 83.3%

6. Secondary Outcome

Title	Kinetics of Immune Reconstitution as Measured by Time to Neutrophil Engraftment (Recipient Only)
Description	-Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.
Time Frame	Up to Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Median (Full Range) [days]	12

7. Secondary Outcome

Title	Kinetics of Immune Reconstitution as Measured by Time to Platelet Engraftment (Recipient Only)
Description	-Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 7 days.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

1 recipient did not have platelet engraftment by Day 180 and is not evaluable for this outcome measure.

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	20
Median (Full Range) [days]	22

8. Secondary Outcome

Title	Rate of Acute Graft vs. Host Disease (GvHD) (Recipient Only)
Description	-Incidence and severity of acute GVHD will be assessed based on the Seattle criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
Time Frame	Up through Day 100

Outcome Measure Data

Analysis Population Description

3 of the recipients received cells mobilized by 10 mcg/kg of GM-CSF and the 11 recipients received stem cells from donors mobilized with the decreased dose of 5 mcg/kg of GM-CSF.

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Count of Participants [Participants]	14 58.3%

9. Secondary Outcome

Title	Rate of Chronic Graft vs. Host Disease (GvHD) (Recipient Only)
Description	Incidence and severity of chronic GVHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
Time Frame	Day 100-1 year

Outcome Measure Data

Analysis Population Description

6 participants are not evaluable for this outcome measure as they came off study prior to the start of chronic GvHD assessments.

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	15
Count of Participants [Participants]	10 41.7%

10. Secondary Outcome

Title	Transplant Related Mortality (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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Count of Participants [Participants]	2 8.3%

11. Secondary Outcome

Title	Relapse and Disease Progression Rate
Description	-A patient will be considered relapsed (disease progressed) when there is a recurrence of the original malignant disease after transplantation.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Count of Participants [Participants]	5 20.8%

12. Secondary Outcome

Title	Death of Any Cause (Recipients Only)
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2 - Recipient
Arm/Group Description	Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
Measure Participants	21
Count of Participants [Participants]	9 37.5%

Adverse Events

Arm/Group Title	Arm 1 - Donor		Arm 2 - Recipient
Arm/Group Description	Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.		Conditioning Regimens fludarabine and busulfan +/- thymoglobulin fractionated total body irradiation and cyclophosphamide busulfan and cyclophosphamide single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
All Cause Mortality
	Arm 1 - Donor		Arm 2 - Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 - Donor		Arm 2 - Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		8/21 (38.1%)
Cardiac disorders
Cardiac arrest	0/23 (0%)		1/21 (4.8%)
Gastrointestinal disorders
Diarrhea	0/23 (0%)		1/21 (4.8%)
Nausea	0/23 (0%)		1/21 (4.8%)
Vomiting	0/23 (0%)		1/21 (4.8%)
General disorders
Fatigue	0/23 (0%)		1/21 (4.8%)
Rigors	0/23 (0%)		1/21 (4.8%)
Infections and infestations
Enterocolitis infectious	0/23 (0%)		1/21 (4.8%)
Lung infection	0/23 (0%)		1/21 (4.8%)
Sepsis	0/23 (0%)		2/21 (9.5%)
Sinusitis	0/23 (0%)		1/21 (4.8%)
Investigations
Transamintis	0/23 (0%)		1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/23 (4.3%)		0/21 (0%)
Skin and subcutaneous tissue disorders
Rash	0/23 (0%)		1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Arm 1 - Donor		Arm 2 - Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/23 (100%)		21/21 (100%)
Blood and lymphatic system disorders
Anemia	11/23 (47.8%)		7/21 (33.3%)
Febrile neutropenia	0/23 (0%)		9/21 (42.9%)
Hemolytic anemia	0/23 (0%)		1/21 (4.8%)
Cardiac disorders
Atrial fibrillation	0/23 (0%)		2/21 (9.5%)
Chest pain - cardiac	1/23 (4.3%)		0/21 (0%)
Heart failure	0/23 (0%)		1/21 (4.8%)
Heart racing	0/23 (0%)		1/21 (4.8%)
Palpitations	1/23 (4.3%)		1/21 (4.8%)
Pericarditis	0/23 (0%)		1/21 (4.8%)
Sinus bradycardia	3/23 (13%)		2/21 (9.5%)
Sinus tachycardia	1/23 (4.3%)		2/21 (9.5%)
Supraventricular tachycardia	0/23 (0%)		1/21 (4.8%)
Eye disorders
Conjunctivitis	1/23 (4.3%)		0/21 (0%)
Visual disturbance (purple lights)	0/23 (0%)		1/21 (4.8%)
Gastrointestinal disorders
Abdominal distension	0/23 (0%)		2/21 (9.5%)
Abdominal pain	4/23 (17.4%)		2/21 (9.5%)
Anal pain	0/23 (0%)		1/21 (4.8%)
Bloating	1/23 (4.3%)		0/21 (0%)
Colitis	0/23 (0%)		1/21 (4.8%)
Constipation	1/23 (4.3%)		3/21 (14.3%)
Diarrhea	10/23 (43.5%)		17/21 (81%)
Dyspepsia	1/23 (4.3%)		1/21 (4.8%)
Dysphagia	0/23 (0%)		2/21 (9.5%)
Esophageal pain	0/23 (0%)		1/21 (4.8%)
Gastroesophageal reflux disease	1/23 (4.3%)		1/21 (4.8%)
Gastrointestinal pain	0/23 (0%)		1/21 (4.8%)
Hemorrhoids	0/23 (0%)		2/21 (9.5%)
Ileus	0/23 (0%)		1/21 (4.8%)
Mucositis oral	1/23 (4.3%)		14/21 (66.7%)
Nausea	8/23 (34.8%)		14/21 (66.7%)
Oral dysesthesia	1/23 (4.3%)		0/21 (0%)
Oral pain	0/23 (0%)		1/21 (4.8%)
Rectal pain	0/23 (0%)		1/21 (4.8%)
Salivary duct inflammation	1/23 (4.3%)		0/21 (0%)
Stomach pain	0/23 (0%)		1/21 (4.8%)
Tonsilitis	0/23 (0%)		1/21 (4.8%)
Vomiting	3/23 (13%)		4/21 (19%)
General disorders
Catheter site swelling	0/23 (0%)		1/21 (4.8%)
Catheter site tenderness	0/23 (0%)		1/21 (4.8%)
Chills	0/23 (0%)		4/21 (19%)
Diaphoresis	1/23 (4.3%)		0/21 (0%)
Edema face	0/23 (0%)		1/21 (4.8%)
Edema limbs	0/23 (0%)		9/21 (42.9%)
Facial pain	1/23 (4.3%)		2/21 (9.5%)
Fatigue	9/23 (39.1%)		11/21 (52.4%)
Fever	1/23 (4.3%)		4/21 (19%)
Flu-like symptoms	3/23 (13%)		0/21 (0%)
Infusion site extravasation	0/23 (0%)		1/21 (4.8%)
Injection site reaction	7/23 (30.4%)		0/21 (0%)
Left chest fasciculations	1/23 (4.3%)		0/21 (0%)
Localized edema	1/23 (4.3%)		1/21 (4.8%)
Non-cardiac chest pain	2/23 (8.7%)		4/21 (19%)
Pain	2/23 (8.7%)		1/21 (4.8%)
Pain at catheter placement site	1/23 (4.3%)		0/21 (0%)
Hepatobiliary disorders
Cholecystitis	0/23 (0%)		1/21 (4.8%)
Hepatic failure	0/23 (0%)		1/21 (4.8%)
Immune system disorders
Allergic reaction	0/23 (0%)		1/21 (4.8%)
Infections and infestations
Catheter related infection	0/23 (0%)		1/21 (4.8%)
Enterocolitis infectious	0/23 (0%)		1/21 (4.8%)
Gum infection	0/23 (0%)		1/21 (4.8%)
HSV stomatitis	0/23 (0%)		1/21 (4.8%)
Lung infection	0/23 (0%)		1/21 (4.8%)
Nail infection	0/23 (0%)		1/21 (4.8%)
Oral HSV	0/23 (0%)		1/21 (4.8%)
Sepsis	0/23 (0%)		2/21 (9.5%)
Skin infection	1/23 (4.3%)		2/21 (9.5%)
Stool VRE	0/23 (0%)		1/21 (4.8%)
Urinary tract infection	0/23 (0%)		1/21 (4.8%)
Injury, poisoning and procedural complications
Bruising	0/23 (0%)		1/21 (4.8%)
Hip fracture	0/23 (0%)		1/21 (4.8%)
Spinal fracture	0/23 (0%)		1/21 (4.8%)
Vascular access complication	7/23 (30.4%)		0/21 (0%)
Investigations
Activated partial thromboplastin time prolonged	1/23 (4.3%)		2/21 (9.5%)
Alanine aminotransferase increased	0/23 (0%)		6/21 (28.6%)
Alkaline phosphatase increased	0/23 (0%)		3/21 (14.3%)
Aspartate aminotransferase increased	0/23 (0%)		4/21 (19%)
Blood bilirubin increased	0/23 (0%)		9/21 (42.9%)
Creatinine increased	1/23 (4.3%)		6/21 (28.6%)
Ejection fraction decreased	0/23 (0%)		1/21 (4.8%)
Hypernatremia	0/23 (0%)		2/21 (9.5%)
Hyperuricemia	0/23 (0%)		4/21 (19%)
INR increased	1/23 (4.3%)		2/21 (9.5%)
Lymphocyte count decreased	1/23 (4.3%)		2/21 (9.5%)
Lymphocyte count increased	0/23 (0%)		2/21 (9.5%)
Neutrophil count decreased	1/23 (4.3%)		8/21 (38.1%)
Platelet count decreased	14/23 (60.9%)		13/21 (61.9%)
White blood cell count decreased	1/23 (4.3%)		6/21 (28.6%)
Metabolism and nutrition disorders
Acidosis	0/23 (0%)		1/21 (4.8%)
Anorexia	3/23 (13%)		7/21 (33.3%)
Hyperglycemia	1/23 (4.3%)		2/21 (9.5%)
Hyperkalemia	0/23 (0%)		6/21 (28.6%)
Hypoalbuminemia	0/23 (0%)		3/21 (14.3%)
Hypocalcemia	1/23 (4.3%)		4/21 (19%)
Hypokalemia	0/23 (0%)		2/21 (9.5%)
Hypomagnesemia	0/23 (0%)		5/21 (23.8%)
Hyponatremia	1/23 (4.3%)		4/21 (19%)
Hypophosphatemia	0/23 (0%)		2/21 (9.5%)
Phosphate increased	0/23 (0%)		1/21 (4.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/23 (30.4%)		2/21 (9.5%)
Back pain	9/23 (39.1%)		4/21 (19%)
Bone pain	7/23 (30.4%)		3/21 (14.3%)
Chest wall pain	5/23 (21.7%)		0/21 (0%)
Dislocation Left Hip Hemiarthroplasty	0/23 (0%)		1/21 (4.8%)
Fall	0/23 (0%)		1/21 (4.8%)
Flank pain	1/23 (4.3%)		0/21 (0%)
Generalized muscle weakness	1/23 (4.3%)		1/21 (4.8%)
Myalgia	2/23 (8.7%)		0/21 (0%)
Neck pain	1/23 (4.3%)		1/21 (4.8%)
Pain in extremity	6/23 (26.1%)		5/21 (23.8%)
Nervous system disorders
Cognitive disturbance	0/23 (0%)		1/21 (4.8%)
Dizziness	7/23 (30.4%)		3/21 (14.3%)
Headache	9/23 (39.1%)		10/21 (47.6%)
Hypersomnia	0/23 (0%)		1/21 (4.8%)
Paresthesia	4/23 (17.4%)		0/21 (0%)
Peripheral sensory neuropathy	3/23 (13%)		1/21 (4.8%)
Presyncope	4/23 (17.4%)		0/21 (0%)
Seizure	0/23 (0%)		1/21 (4.8%)
Somnolence	0/23 (0%)		2/21 (9.5%)
Tremor	0/23 (0%)		1/21 (4.8%)
Psychiatric disorders
Anxiety	5/23 (21.7%)		1/21 (4.8%)
Confusion	0/23 (0%)		2/21 (9.5%)
Depression	1/23 (4.3%)		1/21 (4.8%)
Excessive dreams	0/23 (0%)		1/21 (4.8%)
Insomnia	0/23 (0%)		2/21 (9.5%)
Renal and urinary disorders
Acute kidney injury	0/23 (0%)		3/21 (14.3%)
Renal colic	1/23 (4.3%)		0/21 (0%)
Urinary tract pain	1/23 (4.3%)		0/21 (0%)
Urinary tract pain	0/23 (0%)		2/21 (9.5%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/23 (4.3%)		1/21 (4.8%)
Aspiration	0/23 (0%)		1/21 (4.8%)
Atelectasis	0/23 (0%)		1/21 (4.8%)
Cough	2/23 (8.7%)		3/21 (14.3%)
Dyspnea	1/23 (4.3%)		4/21 (19%)
Epistaxis	0/23 (0%)		2/21 (9.5%)
Hiccups	0/23 (0%)		2/21 (9.5%)
Hypoxia	0/23 (0%)		3/21 (14.3%)
Laryngeal inflammation	0/23 (0%)		1/21 (4.8%)
Nasal congestion	2/23 (8.7%)		0/21 (0%)
Pleural effusion	0/23 (0%)		1/21 (4.8%)
Pleuritic pain	0/23 (0%)		1/21 (4.8%)
Pulmonary edema	0/23 (0%)		1/21 (4.8%)
Sore throat	3/23 (13%)		5/21 (23.8%)
Skin and subcutaneous tissue disorders
GVHD - Skin (Rash)	0/23 (0%)		1/21 (4.8%)
Hypohidrosis	0/23 (0%)		1/21 (4.8%)
Jaundice	0/23 (0%)		1/21 (4.8%)
Pruritus	0/23 (0%)		3/21 (14.3%)
Rash - GVHD (Chest)	0/23 (0%)		1/21 (4.8%)
Rash - GVHD (Palms)	0/23 (0%)		1/21 (4.8%)
Rash - GVHD (Skin in general)	0/23 (0%)		1/21 (4.8%)
Rash maculo-papular	0/23 (0%)		7/21 (33.3%)
Skin ulceration	0/23 (0%)		3/21 (14.3%)
Vascular disorders
Flushing	1/23 (4.3%)		1/21 (4.8%)
Hot flashes	1/23 (4.3%)		0/21 (0%)
Hypertension	1/23 (4.3%)		5/21 (23.8%)
Hypotension	5/23 (21.7%)		2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

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.