Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00860574
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH)
• Enrollment: 96
• Locations: 3
• Arm: 1
• Patients Per Site: 32

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor bone marrow or peripheral blood 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 and methotrexate before and after transplant may stop this from happening

Condition or Disease	Intervention/Treatment	Phase
Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia	Drug: treosulfan; Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: peripheral blood stem cell transplantation; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: methotrexate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Decrease the incidence of relapse to < 15% at 6 month post transplant in patients with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transplanted from related or unrelated donors, without unacceptably increasing toxicity (10% non-relapse mortality [NRM] at 6 months).

SECONDARY OBJECTIVES:

1. Evaluate the incidence of NRM at 180 days and 1 year after hematopoietic cell transplantation (HCT).

2. Evaluate overall survival (OS) and relapse-free survival (RFS). III. Incidence of grades II-IV acute graft-versus-host disease (GVHD). IV. Incidence of chronic GVHD. V. Donor chimerism on days +28 and +100.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally (PO) twice daily (BID) on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Study of Conditioning With Treosulfan, Fludarabine and Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia (ALL)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Feb 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (allogeneic transplantation) CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Drug: treosulfan; Given IV; Other Names: dihydroxybusulfan Ovastat tresulfon ; Drug: fludarabine phosphate; Given IV; Other Names: 2-F-ara-AMP Beneflur Fludara ; Radiation: total-body irradiation; Low dose starting at 2Gy; Other Names: TBI ; Procedure: peripheral blood stem cell transplantation; Given IV per institutional standard practice; Other Names: PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ; Drug: tacrolimus; Given IV or PO; Other Names: FK 506 Prograf ; Procedure: allogeneic bone marrow transplantation; Given IV per institutional standard practice; Other Names: bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow ; Procedure: allogeneic hematopoietic stem cell transplantation; Given IV per institutional standard practice; Drug: methotrexate; Given IV; Other Names: amethopterin Folex methylaminopterin Mexate MTX

Outcome Measures

Primary Outcome Measures

1. Relapse Incidence [At 6 months]

2. Non Relapse Mortality (NRM) Incidence [At 6 months]

   Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression.

Secondary Outcome Measures

1. Non Relapse Mortality Incidence [1 year after HCT]

2. Overall Survival (OS) [at 2 years]

3. Relapse-free Survival [at 2 years]

4. Incidence of Grades II-IV Acute GVHD [at 6 months]

5. Incidence of Chronic GVHD [at 6 months]

6. Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood [Day 28 after HCT]

   Donor chimerism was evaluated in peripheral blood T cells

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute myeloid leukemia (AML):

• All AML patients beyond 1st remission;

• Intermediate or high risk AML patients (based on South West Oncology Group [SWOG] cytogenetic criteria) in 1st complete remission

• Myelodysplastic syndrome (MDS)

• Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference [PCC])

• 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)

• Previous autologous or allogeneic HCT is allowed

• Donors must be:

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

• Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele, except for HLA-C where no mismatch is allowed

• Able to undergo peripheral blood stem cell collection or bone marrow harvest

• In good general health, with a Karnofsky or Lansky Play Performance score > 90%

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

• Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

Exclusion Criteria:

• Receiving umbilical cord blood

• With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac insufficiency requiring treatment or symptomatic coronary artery disease

• With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous oxygen

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

• With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 x upper normal limit 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 because of possible risk of lethal infection when treated with immunosuppressive therapy

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

• With life expectancy severely limited by diseases other than malignancy

• Women who are pregnant or lactating because of possible risk to the fetus or infant

• With known hypersensitivity to treosulfan and/or fludarabine

• 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

• Ineligible donors will be those:

• Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis

• Who are HIV-positive

• With active infectious hepatitis

• Females with a positive pregnancy test

• 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	University of Colorado	Denver	Colorado	United States	80217-3364
2	Oregon Health and Science University	Portland	Oregon	United States	97239
3	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Boglarka Gyurkocza, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joachim Deeg, Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00860574
• Other Study ID Numbers: 2272.00; NCI-2010-00315; P01HL036444
• First Posted: Mar 12, 2009
• Last Update Posted: Jun 22, 2021
• Last Verified: Feb 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Myelodysplastic Syndromes; Syndrome; Recurrence; Methotrexate; Fludarabine phosphate; Fludarabine; Treosulfan; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Period Title: Overall Study
STARTED	96
COMPLETED	93
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6 and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Overall Participants	96
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	39 40.6%
Male	57 59.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.1%
Not Hispanic or Latino	93 96.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.1%
Asian	2 2.1%
Native Hawaiian or Other Pacific Islander	2 2.1%
Black or African American	1 1%
White	87 90.6%
More than one race	2 2.1%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	96 100%

Outcome Measures

1. Primary Outcome

Title	Relapse Incidence
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	18 18.8%

2. Primary Outcome

Title	Non Relapse Mortality (NRM) Incidence
Description	Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	6 6.3%

3. Secondary Outcome

Title	Non Relapse Mortality Incidence
Time Frame	1 year after HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	6 6.3%

4. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	at 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	71 74%

5. Secondary Outcome

Title	Relapse-free Survival
Time Frame	at 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	62 64.6%

6. Secondary Outcome

Title	Incidence of Grades II-IV Acute GVHD
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	57 59.4%

7. Secondary Outcome

Title	Incidence of Chronic GVHD
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	96
Count of Participants [Participants]	20 20.8%

8. Secondary Outcome

Title	Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood
Description	Donor chimerism was evaluated in peripheral blood T cells
Time Frame	Day 28 after HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
Measure Participants	87
Median (Full Range) [percentage of T cells]	100

Adverse Events

Time Frame	Toxicities Before Day 100
Adverse Event Reporting Description	Toxicities documented per Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Arm/Group Title	Treatment (Allogeneic Transplantation)
Arm/Group Description	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6 and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV
All Cause Mortality
	Treatment (Allogeneic Transplantation)
	Affected / at Risk (%)	# Events
Total	21/96 (21.9%)
Serious Adverse Events
	Treatment (Allogeneic Transplantation)
	Affected / at Risk (%)	# Events
Total	17/96 (17.7%)
Cardiac disorders
Heart failure	1/96 (1%)
Hypotension	1/96 (1%)
Gastrointestinal disorders
Mucositis	4/96 (4.2%)
Gut GVHD	1/96 (1%)
Hepatobiliary disorders
Bilirubin	1/96 (1%)
Liver failure	1/96 (1%)
AST 2680	1/96 (1%)
Infections and infestations
Bacterial/sepsis	1/96 (1%)
Sepsis	4/96 (4.2%)
VRE bacteremia/sepsis	1/96 (1%)
Disseminated toxoplasmosis	1/96 (1%)
Enterococcal bacteremia/VRE	1/96 (1%)
CMV pneumonia	1/96 (1%)
Aspirgillus	1/96 (1%)
Metabolism and nutrition disorders
Hyperglycemia	2/96 (2.1%)
Hypoglycemia w/seizures	1/96 (1%)
Hyponatremia	1/96 (1%)
Psychiatric disorders
Apnea	1/96 (1%)
Renal and urinary disorders
Kidney rejection - pre-existing hx kidney transplant	1/96 (1%)
Renal failure/dialysis	1/96 (1%)
Renal failure	1/96 (1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome (ARDS)	1/96 (1%)
Hypoxia/resp failure	2/96 (2.1%)
Pneumonitis	1/96 (1%)
Intubated secondary to DAH	1/96 (1%)
Respiratory failure/intubated	1/96 (1%)
Cardiac arrythmia	1/96 (1%)
Pul.Edema	1/96 (1%)
Pneumonia	1/96 (1%)
Diffuse alveolar hemorrhage	1/96 (1%)
Other (Not Including Serious) Adverse Events
	Treatment (Allogeneic Transplantation)
	Affected / at Risk (%)	# Events
Total	68/96 (70.8%)
Blood and lymphatic system disorders
Deep vein thrombosis	1/96 (1%)
Thrombotic thrombocytopenic purpura (TTP) coagulation	1/96 (1%)
Cardiac disorders
Atrial Fibrillation	3/96 (3.1%)
Edema	1/96 (1%)
Hypotension	4/96 (4.2%)
LVEF 35%	1/96 (1%)
Sinus tachycardia	1/96 (1%)
Eye disorders
Retinal central vein occlusion	1/96 (1%)
Gastrointestinal disorders
Mucositis	23/96 (24%)
Mucosi	2/96 (2.1%)
Nausea	5/96 (5.2%)
Vomiting	4/96 (4.2%)
Diarrhea	11/96 (11.5%)
Diverticulitis	1/96 (1%)
Anorexia	1/96 (1%)
Other	1/96 (1%)
Abdominal pain	1/96 (1%)
GI bleed	1/96 (1%)
General disorders
Fatigue	6/96 (6.3%)
Adrenal insufficiency	1/96 (1%)
Dehydration	2/96 (2.1%)
Proximal myopathy	1/96 (1%)
Steroid induced DM	1/96 (1%)
LE weakness/deconditioning	1/96 (1%)
Fall	1/96 (1%)
Malnutrition	1/96 (1%)
Hepatobiliary disorders
ALT/AST	1/96 (1%)
ALT	1/96 (1%)
AST	2/96 (2.1%)
t.bili 4.2	1/96 (1%)
Bilirubin	1/96 (1%)
Infections and infestations
Infections	56/96 (58.3%)
Metabolism and nutrition disorders
Hyperglycemia	6/96 (6.3%)
Elevated ferritin	1/96 (1%)
Hyperkalemia	1/96 (1%)
Musculoskeletal and connective tissue disorders
Pain	6/96 (6.3%)
Myalgia	2/96 (2.1%)
Steroid myopathy	2/96 (2.1%)
Nervous system disorders
Neuropathic leg pain	1/96 (1%)
Syncope	2/96 (2.1%)
Peripheral neuropathy	1/96 (1%)
Posterior reversible encephalopathy syndrome (PRES)	1/96 (1%)
Psychiatric disorders
Confusion	4/96 (4.2%)
Altered Mental Status	2/96 (2.1%)
Hallucinations	1/96 (1%)
Renal and urinary disorders
Dysuria	1/96 (1%)
Acute renal failure/creatinine	2/96 (2.1%)
Creatinine	1/96 (1%)
Renal failure/acidosis	1/96 (1%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	8/96 (8.3%)
Pleural effusion	2/96 (2.1%)
Dyspnea	1/96 (1%)
Pulmonary Embolism	1/96 (1%)
Skin and subcutaneous tissue disorders
Rash	11/96 (11.5%)

Limitations/Caveats

[Not Specified]

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.