Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01894477
• Collaborator: National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 103
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well treosulfan and fludarabine phosphate, with or without total body irradiation before donor stem cell transplant works in treating patients with myelodysplastic syndrome or acute myeloid leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and mycophenolate mofetil after the transplant may stop this from happening.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable	Procedure: Allogeneic Bone Marrow Transplantation; Drug: Fludarabine Phosphate; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Total-Body Irradiation; Drug: Treosulfan; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the better of two treosulfan-based conditioning regimens in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), by comparing 6-month progression-free survival.

SECONDARY OBJECTIVES:

1. Determine the effects of two conditioning regimens on changes in gene expression profiles, and evaluate the association of gene expression profiles and disease relapse.

2. Determine the incidence of progression-free survival at 1 year and 2 years after hematopoietic cell transplantation (HCT).

3. Evaluate overall survival (OS) at 6 months, at 1 year and at 2 years after HCT.

4. Determine the incidence of grades II-IV acute graft-versus-host disease (GVHD).

5. Determine the incidence of chronic GVHD.

6. Determine donor chimerism around days +28 and +84.

CONDITIONING REGIMEN:

Arm A: Patients receive treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

Arm B: Patients receive treosulfan and fludarabine phosphate as in Arm A and undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANT: Patients in both arms undergo allogeneic peripheral blood stem cell (PBSC) transplant or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Patients with a related donor receive tacrolimus orally (PO) every 8 or 12 hours on days -3 to 56 with taper to day 180. Beginning 4-6 hours after PBSC infusion, patients also receive mycophenolate mofetil PO every 12 hours to day 28. Patients with an unrelated donor receive tacrolimus PO every 8 or 12 hours on days -3 to 100 with taper to day 180. Beginning 4-6 hours after PBSC infusion, patients also receive mycophenolate mofetil PO every 8 hours to day 40 with taper to day 96.

NOTE: Patients with related donors eligible for FHCRC protocol 2545 may receive cyclosporine IV, instead of tacrolimus, beginning on day -3 to day 50 with a taper to day 180.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Treosulfan, Fludarabine and Low-Dose TBI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jan 9, 2017
• Anticipated Study Completion Date: Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Arm A: Treosulfan, Fludarabine Phosphate Treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.	Procedure: Allogeneic Bone Marrow Transplantation; Undergo allogeneic bone marrow transplant; Other Names: Allo BMT Allogeneic BMT ; Drug: Fludarabine Phosphate; Intravenously administered Fludarabine Phosphate; Other Names: 2-F-ara-AMP Beneflur Fludara SH T 586 ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo allogeneic PBSC transplant; Other Names: PBPC transplantation Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplantation ; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation ; Drug: Treosulfan; Intravenously administered Treosulfan; Other Names: 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]- Dihydroxybusulfan Ovastat Treosulphan Tresulfon ; Other: Laboratory Biomarker Analysis; Correlative Studies
Experimental: Arm B Arm B: Treosulfan, Fludarabine Phosphate, TBI Treosulfan and fludarabine phosphate as in Arm A and undergo low -dose total-body irradiation (TBI) on day 0	Procedure: Allogeneic Bone Marrow Transplantation; Undergo allogeneic bone marrow transplant; Other Names: Allo BMT Allogeneic BMT ; Drug: Fludarabine Phosphate; Intravenously administered Fludarabine Phosphate; Other Names: 2-F-ara-AMP Beneflur Fludara SH T 586 ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo allogeneic PBSC transplant; Other Names: PBPC transplantation Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplantation ; Drug: Treosulfan; Intravenously administered Treosulfan; Other Names: 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]- Dihydroxybusulfan Ovastat Treosulphan Tresulfon ; Other: Laboratory Biomarker Analysis; Correlative Studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Did Not Progress Within 6 Months [At 6 months post-transplant]

   Progression is defined as relapse

Secondary Outcome Measures

1. Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [Up to 84 days]

2. Incidence of Chronic GVHD Graded by the NCI CTCAE Version 4.0 [Up to 5 year]

3. Incidence of Relapse/Progression [Up to 5 year]

4. NRM [Up to 5 years]

5. Overall Survival (OS) [Up to 2 year]

6. Change in Gene Expression Profiles [Baseline and at day 0 within 6 hours of conditioning prior to transplant]

   Differences between arms in the changes in gene expression will be compared. 80% power to detect mean differences of approximately 1.4 standard deviation units, at the 2-sided 0.05 level of significance (with Bonferroni correction for 50 genes).

7. Relapse Risk as Measured by Degree of Change in Gene Expression Profiles [Baseline and at day 0 within 6 hours of conditioning prior to transplant]

   Among genes identified whose expression is modified by conditioning, degree of change in expression will be evaluated to determine if it is correlated with relapse risk and offers improved prediction of relapse risk over that obtained with standard clinical parameters (cytogenetics, blast count, International Prognostic Scoring System score, minimal residual disease. To account for censoring and the competing risk of non-relapse mortality (NRM), the analysis will be a time-to-event analysis of relapse using Cox regression, with change in expression as a continuous covariate (on a log scale). 8

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• MDS, myelodysplastic syndrome/myeloproliferative neoplasia overlap disorders (including chronic myelomonocytic leukemia [CMML], and MDS/myeloproliferative neoplasm [MPN] unclassifiable syndromes)

• AML, other than acute promyelocytic leukemia (APL), in first or second remission or with minimal residual disease

• With Karnofsky index or Lansky Play-Performance scale > 70% on pre-transplant evaluation

• Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)

• Patients with previous autologous or allogeneic HCT are allowed to enroll

• DONOR: Human leukocyte antigen (HLA)-identical related donors or

• DONOR: Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for one HLA allele is allowed

• DONOR: Donors able to undergo peripheral blood stem cell collection or bone marrow harvest

• DONOR: Donors in good general health, with a Karnofsky or Lansky play performance score > 90%

• DONOR: Donors able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)

Exclusion Criteria:

• Receiving umbilical cord blood

• With impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist

• With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and carbon monoxide diffusing capability test (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O2) saturation < 92% on room air), or receiving supplementary continuous oxygen

• With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2 x upper limit of normal or dialysis-dependent

• With hepatic dysfunction as evidenced by total bilirubin > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis

• With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis

• With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist

• With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis

• With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6)

• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy

• With life expectancy severely limited by diseases other than malignancy

• Women who are pregnant or lactating

• With known hypersensitivity to treosulfan or fludarabine (fludarabine phosphate)

• Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)

• Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent

• DONOR: Individuals deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis

• DONOR: Individuals who are HIV-positive

• DONOR: Individuals with active infectious hepatitis

• DONOR: Females with a positive pregnancy test

• DONOR: Persons unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: H. Joachim Deeg, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joachim Deeg, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01894477
• Other Study ID Numbers: 2524.00; NCI-2013-01261; 2524; 2524.00; K12HL087165; P30CA015704
• First Posted: Jul 10, 2013
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Neoplasm, Residual; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Fludarabine; Fludarabine phosphate; Treosulfan; Busulfan

Study Results

Participant Flow

Arm/Group Title	Arm A (Treosulfan, Fludarabine Phosphate)	Arm B (Treosulfan, Fludarabine Phosphate, TBI)
Arm/Group Description	CONDITIONING REGIMEN: Treosulfan IV over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: Patients in both arms undergo allogeneic PBSC transplant or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients with related donor receive tacrolimus PO every 8 or 12 hours on days -3 to 56 with taper to day 180. Beginning 4-6 hours after PBSC infusion, and mycophenolate mofetil PO every 12 hours to day 28. Patients with an unrelated donor receive tacrolimus PO every 8 or 12 hours on days -3 to 100 with taper to day 180. Beginning 4-6 hours after PBSC infusion, and mycophenolate mofetil PO every 8 hours to day 40 with taper to day 96. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC	CONDITIONING REGIMEN: Treosulfan and fludarabine phosphate as in Arm A and undergo low-dose TBI on day 0. TRANSPLANT: Patients in both arms undergo allogeneic PBSC transplant or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients with a related donor receive tacrolimus PO every 8 or 12 hours on days -3 to 56 with taper to day 180. Beginning 4-6 hours after PBSC infusion, and mycophenolate mofetil PO every 12 hours to day 28. Patients with an unrelated donor receive tacrolimus PO every 8 or 12 hours on days -3 to 100 with taper to day 180. Beginning 4-6 hours after PBSC infusion, and mycophenolate mofetil PO every 8 hours to day 40 with taper to day 96. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Fludarabine Phosphate: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC transplant Total-Body Irradation
Period Title: Overall Study
STARTED	35	67
COMPLETED	35	65
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Arm A (Treosulfan, Fludarabine Phosphate)	Arm B (Treosulfan, Fludarabine Phosphate, TBI)	Total
Arm/Group Description	Treosulfan IV over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.	Treosulfan and fludarabine phosphate as in Arm A and undergo low-dose TBI on day 0.	Total of all reporting groups
Overall Participants	35	65	100
Age (Count of Participants)
<=18 years	0 0%	2 3.1%	2 2%
Between 18 and 65 years	28 80%	53 81.5%	81 81%
>=65 years	7 20%	10 15.4%	17 17%
Sex: Female, Male (Count of Participants)
Female	18 51.4%	31 47.7%	49 49%
Male	17 48.6%	34 52.3%	51 51%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 3.1%	2 2%
Not Hispanic or Latino	35 100%	62 95.4%	97 97%
Unknown or Not Reported	0 0%	1 1.5%	1 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.9%	1 1.5%	2 2%
Asian	2 5.7%	9 13.8%	11 11%
Native Hawaiian or Other Pacific Islander	1 2.9%	1 1.5%	2 2%
Black or African American	0 0%	1 1.5%	1 1%
White	30 85.7%	52 80%	82 82%
More than one race	1 2.9%	0 0%	1 1%
Unknown or Not Reported	0 0%	1 1.5%	1 1%
Region of Enrollment (participants) [Number]
United States	35 100%	63 96.9%	98 98%
Indonesia	0 0%	1 1.5%	1 1%
Samoa	0 0%	1 1.5%	1 1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Did Not Progress Within 6 Months
Description	Progression is defined as relapse
Time Frame	At 6 months post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Treosulfan, Fludarabine Phosphate)	Arm B (Treosulfan, Fludarabine Phosphate, TBI)
Arm/Group Description	Treosulfan IV over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.	Treosulfan and fludarabine phosphate as in Arm A and undergo low-dose TBI on day 0.
Measure Participants	35	65
Count of Participants [Participants]	20 57.1%	48 73.8%

2. Secondary Outcome

Title	Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time Frame	Up to 84 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Treosulfan, Fludarabine Phosphate)	Arm B (Treosulfan, Fludarabine Phosphate, TBI)
Arm/Group Description	Treosulfan IV over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.	Treosulfan and fludarabine phosphate as in Arm A and undergo low-dose TBI on day 0.
Measure Participants	35	65
Count of Participants [Participants]	29 82.9%	50 76.9%

3. Secondary Outcome

Title	Incidence of Chronic GVHD Graded by the NCI CTCAE Version 4.0
Time Frame	Up to 5 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Incidence of Relapse/Progression
Time Frame	Up to 5 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	NRM
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	Up to 2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change in Gene Expression Profiles
Description	Differences between arms in the changes in gene expression will be compared. 80% power to detect mean differences of approximately 1.4 standard deviation units, at the 2-sided 0.05 level of significance (with Bonferroni correction for 50 genes).
Time Frame	Baseline and at day 0 within 6 hours of conditioning prior to transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Relapse Risk as Measured by Degree of Change in Gene Expression Profiles
Description	Among genes identified whose expression is modified by conditioning, degree of change in expression will be evaluated to determine if it is correlated with relapse risk and offers improved prediction of relapse risk over that obtained with standard clinical parameters (cytogenetics, blast count, International Prognostic Scoring System score, minimal residual disease. To account for censoring and the competing risk of non-relapse mortality (NRM), the analysis will be a time-to-event analysis of relapse using Cox regression, with change in expression as a continuous covariate (on a log scale). 8
Time Frame	Baseline and at day 0 within 6 hours of conditioning prior to transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Regimen-related toxicity and infection will be evaluated up to the time the patient is discharged from medical care at the transplant institution, or day 100.
Adverse Event Reporting Description	Regimen-related toxicity, greater or equal to grade 3, excluding cytopenias, and infection will be evaluated up to the time the patient is discharged from medical care at the transplant institution, or day 100. Toxicities will be documented per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All patients undergoing HCT are expected to have Grade 3 and 4 pancytopenia as an intended therapeutic effect, and thus this will not be reported as an adverse event.
Arm/Group Title	Arm A (Treosulfan, Fludarabine Phosphate)		Arm B (Treosulfan, Fludarabine Phosphate, TBI)
Arm/Group Description	Treosulfan IV over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.		Treosulfan and fludarabine phosphate as in Arm A and undergo low-dose TBI on day 0.
All Cause Mortality
	Arm A (Treosulfan, Fludarabine Phosphate)		Arm B (Treosulfan, Fludarabine Phosphate, TBI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/35 (42.9%)		20/67 (29.9%)
Serious Adverse Events
	Arm A (Treosulfan, Fludarabine Phosphate)		Arm B (Treosulfan, Fludarabine Phosphate, TBI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/35 (17.1%)		9/67 (13.4%)
Blood and lymphatic system disorders
Post Transplant Lymphoproliferative Disorder	0/35 (0%)	0	1/67 (1.5%)	1
Cardiac disorders
Cardiac tamponade	0/35 (0%)	0	1/67 (1.5%)	1
pericardial effusion	0/35 (0%)	0	1/67 (1.5%)	1
Myocardial infarction	0/35 (0%)	0	1/67 (1.5%)	1
Atrial fibrillation	0/35 (0%)	0	1/67 (1.5%)	1
Eye disorders
loss of vision	1/35 (2.9%)	1	0/67 (0%)	0
Gastrointestinal disorders
GI bleed	0/35 (0%)	0	1/67 (1.5%)	1
Anorexia	0/35 (0%)	0	1/67 (1.5%)	1
Abdominal pain	0/35 (0%)	0	1/67 (1.5%)	1
CMV Gastritis	1/35 (2.9%)	1	0/67 (0%)	0
General disorders
Hepatobiliary disorders
Liver failure	1/35 (2.9%)	1	1/67 (1.5%)	1
Immune system disorders
Engraftment syndrome	1/35 (2.9%)	1	0/67 (0%)	0
Infections and infestations
Infection	2/35 (5.7%)	2	4/67 (6%)	4
Musculoskeletal and connective tissue disorders
Steroid myopathy	0/35 (0%)	0	1/67 (1.5%)	1
Psychiatric disorders
mental status changes	2/35 (5.7%)	2	1/67 (1.5%)	1
Renal and urinary disorders
Renal failure	2/35 (5.7%)	2	1/67 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	1/35 (2.9%)	1	0/67 (0%)	0
Respiratory failure	3/35 (8.6%)	3	3/67 (4.5%)	3
Hypoxia	0/35 (0%)	0	1/67 (1.5%)	1
Diffuse alveolar hemorrhage	0/35 (0%)	0	1/67 (1.5%)	1
Vascular disorders
Hypotension	1/35 (2.9%)	1	0/67 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A (Treosulfan, Fludarabine Phosphate)		Arm B (Treosulfan, Fludarabine Phosphate, TBI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/35 (80%)		51/67 (76.1%)
Blood and lymphatic system disorders
Posttransplant lymphoproliferative disease (PTLD-DLBC)	0/35 (0%)	0	1/67 (1.5%)	1
Cardiac disorders
Atrial fibrillation/flutter	0/35 (0%)	0	3/67 (4.5%)	3
Decreased LVEF	0/35 (0%)	0	2/67 (3%)	2
bradycardia	0/35 (0%)	0	1/67 (1.5%)	1
pericardial effusion	0/35 (0%)	0	1/67 (1.5%)	1
Elevated BNP	0/35 (0%)	0	1/67 (1.5%)	1
Gastrointestinal disorders
Nausea	6/35 (17.1%)	6	14/67 (20.9%)	14
Vomiting	7/35 (20%)	7	9/67 (13.4%)	9
Diarrhea	2/35 (5.7%)	2	2/67 (3%)	2
Anorexia	4/35 (11.4%)	4	7/67 (10.4%)	7
abdominal pain	2/35 (5.7%)	2	2/67 (3%)	2
mucositis	1/35 (2.9%)	1	5/67 (7.5%)	5
Typhilitis	0/35 (0%)	0	1/67 (1.5%)	1
Ascites	1/35 (2.9%)	1	0/67 (0%)	0
Diverticulitis	1/35 (2.9%)	1	0/67 (0%)	0
General disorders
Deconditioned	3/35 (8.6%)	3	2/67 (3%)	2
Edema	2/35 (5.7%)	2	1/67 (1.5%)	1
Fluid overload	0/35 (0%)	0	1/67 (1.5%)	1
Weakness	4/35 (11.4%)	4	4/67 (6%)	4
Hepatobiliary disorders
Elevated total bilirubin	1/35 (2.9%)	1	2/67 (3%)	2
Elevated Alanine transaminase	1/35 (2.9%)	1	0/67 (0%)	0
sinusoidal obstruction syndrome	0/35 (0%)	0	1/67 (1.5%)	1
Immune system disorders
Engraftment syndrome	1/35 (2.9%)	1	0/67 (0%)	0
Infections and infestations
Infections	20/35 (57.1%)	35	33/67 (49.3%)	54
Metabolism and nutrition disorders
Hypocalcemia	1/35 (2.9%)	1	0/67 (0%)	0
Hyponatremia	2/35 (5.7%)	2	3/67 (4.5%)	3
Hypoglycemia	0/35 (0%)	0	1/67 (1.5%)	1
Hyperglycemia	6/35 (17.1%)	6	5/67 (7.5%)	5
Hyperkalemia	0/35 (0%)	0	1/67 (1.5%)	1
Hypermagnesia	1/35 (2.9%)	1	0/67 (0%)	0
Hypoalbuminenia	1/35 (2.9%)	1	0/67 (0%)	0
Musculoskeletal and connective tissue disorders
Steroid myopathy	2/35 (5.7%)	2	3/67 (4.5%)	3
pain	7/35 (20%)	7	7/67 (10.4%)	7
Myalgia/Arthralgia	3/35 (8.6%)	3	2/67 (3%)	2
Compression fracture	1/35 (2.9%)	1	1/67 (1.5%)	1
Arthritis	0/35 (0%)	0	1/67 (1.5%)	1
Septic arthritis	1/35 (2.9%)	1	0/67 (0%)	0
Nervous system disorders
Peripheral neuropathy	1/35 (2.9%)	1	9/67 (13.4%)	9
Headache	2/35 (5.7%)	2	2/67 (3%)	2
Seizure	0/35 (0%)	0	1/67 (1.5%)	1
Syncope	0/35 (0%)	0	1/67 (1.5%)	1
Psychiatric disorders
mental status changes	1/35 (2.9%)	1	3/67 (4.5%)	3
Hallucinations	0/35 (0%)	0	1/67 (1.5%)	1
Renal and urinary disorders
Elevated creatinine	0/35 (0%)	0	1/67 (1.5%)	1
Bladder spasms	1/35 (2.9%)	1	0/67 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia	0/35 (0%)	0	1/67 (1.5%)	1
Pulmonary edema	0/35 (0%)	0	3/67 (4.5%)	3
Pleural effusion	1/35 (2.9%)	1	2/67 (3%)	2
Hypoxia	2/35 (5.7%)	2	6/67 (9%)	6
Dyspnea	0/35 (0%)	0	1/67 (1.5%)	1
Skin and subcutaneous tissue disorders
Rash	3/35 (8.6%)	3	2/67 (3%)	2
Dermatitis	0/35 (0%)	0	1/67 (1.5%)	1
Peeling blisters	1/35 (2.9%)	1	0/67 (0%)	0
pruritus	1/35 (2.9%)	1	0/67 (0%)	0
Palmar-plantar erythrodysesthesia syndrome	1/35 (2.9%)	1	3/67 (4.5%)	3
Vascular disorders
Hypotension	1/35 (2.9%)	1	7/67 (10.4%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.