Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders
Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00919503
Collaborator
medac GmbH (Industry), National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
98
6
2
130.3
16.3
0.1
Study Details
Study Description
Brief Summary
This phase II clinical trial studies how well treosulfan and fludarabine phosphate with or without low dose radiation before donor stem cell transplantation works in treating patients with nonmalignant (noncancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (noncancerous) diseases such as primary immunodeficiency disorders, bone marrow failure syndromes, hemoglobinopathies, and inborn errors of metabolism (metabolic disorders). Powerful chemotherapy drugs and/or radiation are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy and/or radiation which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine phosphate) with or without low dose radiation results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OUTLINE:
CONDITIONING REGIMEN: Patients receive treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 1 hour on days -6 to -2. Patients receive anti-thymocyte globulin IV over 4-6 hours on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1.
TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood (UCB) from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status.
IMMUNOSUPPRESSION: Patients receive a combination of immunosuppressive medications to try and prevent graft-versus-host disease. There are 2 regimens depending on the donor.
Regimen A: Patients undergoing bone marrow or PBSC transplantation receive tacrolimus daily from day -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Regimen B: Patients undergoing UCB transplantation receive cyclosporine on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil on days 0 to 40 followed by a taper until day 96 in the absence of GVHD.
After completion of study treatment, patients are followed up periodically for 5 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
98 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen
Actual Study Start Date
:
Jul 31, 2009
Actual Primary Completion Date
:
Jun 10, 2020
Actual Study Completion Date
:
Jun 10, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regimen A (PBSCT and BMT) CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
Procedure: Allogeneic Bone Marrow Transplantation
Infused IV
Other Names:
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Drug: Fludarabine Phosphate
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Methotrexate
Given IV
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation
Infused IV
Other Names:
Drug: Tacrolimus
Given IV or PO
Other Names:
Drug: Treosulfan
Given IV
Other Names:
|
| Experimental: Regimen B (UBCT) CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. |
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Drug: Cyclosporine
Given IV or PO
Other Names:
Drug: Fludarabine Phosphate
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
Radiation: Total-Body Irradiation
Undergo total body irradiation
Other Names:
Drug: Treosulfan
Given IV
Other Names:
Procedure: Umbilical Cord Blood Transplantation
Single or double unit umbilical cord blood transplant, infused IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Preliminary Efficacy [1 year following transplant]
Number of patients engrafted (>5% donor CD3+ peripheral blood chimerisms) at 1 year following transplant
Secondary Outcome Measures
- Non-relapse Mortality [1 year following transplant]
Number of patients who experienced non-relapse mortality by 1 year following transplant
- Number of Patients With Grade II-IV Acute Graft-versus-host Disease [Day 100 post transplant]
Number of patients diagnosed with overall grade II-IV acute GVHD by Day 100 post transplant
- Number of Patients With of Chronic Graft-versus-host Disease [1 year following transplant]
Number of patients diagnosed with chronic GVHD and requiring systemic immunosuppression within 1 year following transplant
- Donor Chimerism CD3 at 100 Days Post Transplant [Day 100 post transplant]
Number of patients with peripheral blood donor chimerism for CD3 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant.
- Disease Response at One Year Following Hematopoietic Cell Transplantation [1 year following transplant]
Number of patients with no evidence of disease at one year following transplant
- Immune Reconstitution Following Hematopoietic Cell Transplantation [1 year following transplant]
Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant
- Number of Participants With Infections [100 days post transplant]
Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant
- Overall Survival [1 year following transplant]
Number of patients alive at 1 year following transplant
- Donor Chimerism CD33 at Day 100 Post Transplant [100 days post transplant]
Number of patients with peripheral blood donor chimerism for CD33 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
to 49 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with a nonmalignant disease treatable by allogeneic HCT
-
Patients with a known nonmalignant disease that is not clearly defined will need to be discussed with the protocol principal investigator (PI) (Dr. Lauri Burroughs) and potentially the nonmalignant board to determine if they are eligible for HCT on this study
-
DONOR: Human leukocyte antigens (HLA)-identical related donors or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 or mismatched for a single allele at HLA-A, B, C, DRB1 or a single DQB1 antigen or allele mismatch by high resolution deoxyribonucleic acid (DNA) typing
-
DONOR: PBSC is the preferred cell source (when feasible) for fully matched donors; PBSC may also be used for a mismatched donor following discussion with the PI; bone marrow is allowed when PBSC is not feasible or as determined by the PI
-
DONOR: HLA-matched sibling bone marrow in combination with HLA-matched sibling umbilical cord blood if the HLA-matched sibling umbilical cord blood was collected and stored; the HLA-matched sibling bone marrow and cord blood would be matched for HLA-A, B, C, DRB1, and DQB1
-
DONOR: Unrelated Umbilical Cord Blood: Unit selection is based on the cryopreserved total nucleated cell (TNC) dose and matching at HLA-A, B antigen level and DRB1 allele level typing; while HLA-C antigen/allele level typing is not considered in the matching criteria, if available, may be used to optimize unit selection
-
DONOR: Unrelated Umbilical Cord Blood: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci as defined above
-
DONOR: Unrelated Umbilical Cord Blood: Selection of two umbilical cord blood (UCB) units is allowed to provide sufficient cell dose
-
DONOR: Unrelated Umbilical Cord Blood: The UCB unit with the least HLA disparity (with the patient) will be selected first (i.e., selection priority is 6/6 match > 5/6 match> 4/6 match); additional UCB units then may be selected to achieve the required cell dose; if a second unit is required, this unit will be the unit that most closely HLA matches the patient and meets minimum size criteria outlined below of at least 1.5 x 10^7 TNC/kg (i.e. a smaller more closely matched unit will be selected over a larger less well matched unit as long as minimum criteria are met)
-
DONOR: Unrelated Umbilical Cord Blood: Each UCB unit MUST contain at least 1.5 x 10^7 TNC per kilogram recipient weight
-
DONOR: Unrelated Umbilical Cord Blood: The total cell dose of the combined units must be at least 3.0 x 10^7 TNC per kilogram recipient weight
Exclusion Criteria:
-
Patients with idiopathic aplastic anemia and Fanconi anemia; (patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria [PNH] or inherited marrow failure syndromes, except Fanconi anemia, will be allowed)
-
Patients 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
-
Patients with impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (DLCO) < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air)
-
Patients with impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2 x upper normal limit or dialysis-dependent
-
Patients with evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist
-
Patients with an active infectious disease requiring deferral of conditioning; as recommended by an infectious disease specialist
-
Patients who are positive for human immunodeficiency virus (HIV)
-
Females who are pregnant or breast-feeding
-
Patients with a known hypersensitivity to treosulfan and/or fludarabine
-
Receiving another experimental drug within 4 weeks of initiation of conditioning (day -6) unless approved by the PI
-
DONOR: Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
-
DONOR: HIV-positive
-
DONOR: With active infectious hepatitis
-
DONOR: Females with a positive pregnancy test
-
DONOR: HLA-matched sibling cord blood exclusions: Any cord blood units that have not passed donor screening for infectious disease markers as recommended by the National Marrow Donor Project (NMDP) will not be used unless a waiver is signed by the clinical attending allowing use of cord blood unit; cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
-
DONOR: Unrelated Umbilical Cord Blood: Any cord blood units with < 1.5 x 10^7 total nucleated cells per kilogram recipient weight
-
DONOR: Unrelated Umbilical Cord Blood: Any cord blood units that have not passed donor screening for infectious disease markers as recommended by NMDP will not be used unless a waiver is signed by the clinical attending allowing use of cord blood unit; cord blood units are presumed to be CMV negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 2 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 3 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 4 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 5 | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
| 6 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- medac GmbH
- National Cancer Institute (NCI)
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Lauri M. Burroughs, Fred Hutch/University of Washington Cancer Consortium
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Lauri Burroughs,
Associate Professor, Clinical Research Division, Fred Hutch; Director, Non-Malignant Transplant Program,
Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT00919503
Other Study ID Numbers:
- 2256.00
- NCI-2010-01277
- 2256.00
- P30CA015704
- RG2809001
First Posted:
Jun 12, 2009
Last Update Posted:
Aug 13, 2021
Last Verified:
Jul 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Lauri Burroughs,
Associate Professor, Clinical Research Division, Fred Hutch; Director, Non-Malignant Transplant Program,
Fred Hutchinson Cancer Center
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Period Title: Overall Study | ||
| STARTED | 84 | 14 |
| COMPLETED | 84 | 14 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) | Total |
|---|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV | Total of all reporting groups |
| Overall Participants | 84 | 14 | 98 |
| Age (Count of Participants) | |||
| <=18 years |
70
83.3%
|
13
92.9%
|
83
84.7%
|
| Between 18 and 65 years |
14
16.7%
|
1
7.1%
|
15
15.3%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
28
33.3%
|
3
21.4%
|
31
31.6%
|
| Male |
56
66.7%
|
11
78.6%
|
67
68.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
6
7.1%
|
3
21.4%
|
9
9.2%
|
| Not Hispanic or Latino |
77
91.7%
|
10
71.4%
|
87
88.8%
|
| Unknown or Not Reported |
1
1.2%
|
1
7.1%
|
2
2%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
4.8%
|
2
14.3%
|
6
6.1%
|
| Native Hawaiian or Other Pacific Islander |
1
1.2%
|
0
0%
|
1
1%
|
| Black or African American |
8
9.5%
|
1
7.1%
|
9
9.2%
|
| White |
67
79.8%
|
9
64.3%
|
76
77.6%
|
| More than one race |
4
4.8%
|
1
7.1%
|
5
5.1%
|
| Unknown or Not Reported |
0
0%
|
1
7.1%
|
1
1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
84
100%
|
14
100%
|
98
100%
|
Outcome Measures
| Title | Preliminary Efficacy |
|---|---|
| Description | Number of patients engrafted (>5% donor CD3+ peripheral blood chimerisms) at 1 year following transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: Three patients expired without CD3+ chimerisms being performed, therefore could not be analyzed for primary efficacy |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 11 |
| Count of Participants [Participants] |
83
98.8%
|
10
71.4%
|
| Title | Non-relapse Mortality |
|---|---|
| Description | Number of patients who experienced non-relapse mortality by 1 year following transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 14 |
| Count of Participants [Participants] |
2
2.4%
|
5
35.7%
|
| Title | Number of Patients With Grade II-IV Acute Graft-versus-host Disease |
|---|---|
| Description | Number of patients diagnosed with overall grade II-IV acute GVHD by Day 100 post transplant |
| Time Frame | Day 100 post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: 2 patients expired too early for evaluation for acute GVHD and could not be evaluated for this outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 12 |
| Count of Participants [Participants] |
44
52.4%
|
8
57.1%
|
| Title | Number of Patients With of Chronic Graft-versus-host Disease |
|---|---|
| Description | Number of patients diagnosed with chronic GVHD and requiring systemic immunosuppression within 1 year following transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: 3 patients expired too early for evaluation for chronic GVHD and could not be evaluated for this outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 11 |
| Count of Participants [Participants] |
29
34.5%
|
5
35.7%
|
| Title | Donor Chimerism CD3 at 100 Days Post Transplant |
|---|---|
| Description | Number of patients with peripheral blood donor chimerism for CD3 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. |
| Time Frame | Day 100 post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: 3 patients expired without CD3+ chimerisms being performed and could not be evaluated for this outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 11 |
| Greater than equal to 95% |
49
58.3%
|
7
50%
|
| 50 - 94% |
29
34.5%
|
2
14.3%
|
| 5-49% |
6
7.1%
|
1
7.1%
|
| Less than 5% |
0
0%
|
1
7.1%
|
| Title | Disease Response at One Year Following Hematopoietic Cell Transplantation |
|---|---|
| Description | Number of patients with no evidence of disease at one year following transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: 3 patients expired prior to disease response being evaluated and could not be evaluated for this outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 11 |
| Count of Participants [Participants] |
78
92.9%
|
8
57.1%
|
| Title | Immune Reconstitution Following Hematopoietic Cell Transplantation |
|---|---|
| Description | Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen A: 11 patients did not have lymphocyte subsets drawn post-transplant and could not be evaluated for outcome; Regimen B: 3 patients expired prior to lymphocyte subsets being evaluated and 2 patients did not have lymphocyte subsets drawn post-transplant and could not be evaluated for outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 73 | 9 |
| Count of Participants [Participants] |
39
46.4%
|
4
28.6%
|
| Title | Number of Participants With Infections |
|---|---|
| Description | Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant |
| Time Frame | 100 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 14 |
| Count of Participants [Participants] |
57
67.9%
|
9
64.3%
|
| Title | Overall Survival |
|---|---|
| Description | Number of patients alive at 1 year following transplant |
| Time Frame | 1 year following transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 14 |
| Count of Participants [Participants] |
80
95.2%
|
9
64.3%
|
| Title | Donor Chimerism CD33 at Day 100 Post Transplant |
|---|---|
| Description | Number of patients with peripheral blood donor chimerism for CD33 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. |
| Time Frame | 100 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Regimen B: 2 patients expired without CD33+ chimerisms being performed and could not be evaluated for this outcome |
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) |
|---|---|---|
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV |
| Measure Participants | 84 | 12 |
| Greater than equal to 95% |
72
85.7%
|
7
50%
|
| 50-94% |
8
9.5%
|
2
14.3%
|
| 5-49% |
4
4.8%
|
2
14.3%
|
| Less than 5% |
0
0%
|
1
7.1%
|
Adverse Events
| Time Frame | Day 100 post initiation of conditioning therapy | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Events were collected 100 days post initiation of conditioning therapy. All-Cause Mortality was assessed through 10.6 years post transplant (through study completion date 6/10/2020). | |||
| Arm/Group Title | Regimen A (PBSCT and BMT) | Regimen B (UBCT) | ||
| Arm/Group Description | CONDITIONING REGIMEN A : Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing bone marrow or PBSC transplantation receive tacrolimus IV continuously or PO twice daily on days -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Allogeneic Bone Marrow Transplantation: Infused IV Anti-Thymocyte Globulin: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Peripheral Blood Stem Cell Transplantation: Infused IV Tacrolimus: Given IV or PO Treosulfan: Given IV | CONDITIONING REGIMEN B: Patients receive treosulfan IV on days -6 to -4 and fludarabine phosphate IV on days -6 to -2. Patients receive anti-thymocyte globulin IV on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1 . TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. Patients undergoing UCB transplantation receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or PO every 8 hours on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. Anti-Thymocyte Globulin: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV or PO Total-Body Irradiation: Undergo total body irradiation Treosulfan: Given IV Umbilical Cord Blood Transplantation: Single or double unit umbilical cord blood transplant, infused IV | ||
All Cause Mortality |
||||
| Regimen A (PBSCT and BMT) | Regimen B (UBCT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/84 (8.3%) | 6/14 (42.9%) | ||
Serious Adverse Events |
||||
| Regimen A (PBSCT and BMT) | Regimen B (UBCT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/84 (20.2%) | 5/14 (35.7%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Febrile neutropenia: attributed to rATG | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Febrile Neutropenia: with life- threatening sepsis | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Cardiac disorders | ||||
| Cardiac Asystole following central venous catheter placement | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastrointestinal Other: Pneumatosis | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Abdominal Pain | 1/84 (1.2%) | 2 | 0/14 (0%) | 0 |
| Nausea | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Diarrhea (associated with GVHD): >15ml/kg per day with abdominal pain | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| General disorders | ||||
| Fever (not neutropenic): attributed to rATG | 2/84 (2.4%) | 2 | 0/14 (0%) | 0 |
| Fever (not neutropenic) | 2/84 (2.4%) | 2 | 0/14 (0%) | 0 |
| Immune system disorders | ||||
| Anaphylaxis reaction (rATG) | 2/84 (2.4%) | 2 | 0/14 (0%) | 0 |
| Infections and infestations | ||||
| Sepsis with multiorgan failure | 0/84 (0%) | 0 | 2/14 (14.3%) | 2 |
| Infections and infestations -Other, specify: parainfluenza or sinusitis | 1/84 (1.2%) | 2 | 0/14 (0%) | 0 |
| Infections and infestations -Other, specify: CMV meningitis/encephalo | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Infections and infestations -Other, specify: Clostridium septicum sepsis | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury (reversible, requiring CRRT/dialysis) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonitis | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Apnea: Requiring intubation following BAL; attributed to underlying infection | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Adult respiratory distress syndrome (ARDS) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Dyspnea | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Hypoxia: Decreased O2 sat requiring support | 4/84 (4.8%) | 4 | 0/14 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension: requiring intervention | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Hypotension: shock, pressors | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Regimen A (PBSCT and BMT) | Regimen B (UBCT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/84 (63.1%) | 10/14 (71.4%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombotic microangiopathy (requiring intervention) with acute renal fail: Hemolytic uremic syndrome | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Febrile neutropenia | 14/84 (16.7%) | 17 | 4/14 (28.6%) | 4 |
| Hemolysis (AIHA): Requiring transfusion and sterioids | 2/84 (2.4%) | 2 | 0/14 (0%) | 0 |
| Thrombotic microangiopathy (not requiring intervention) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Febrile neutropenia: attributed to rATG | 7/84 (8.3%) | 7 | 0/14 (0%) | 0 |
| Cardiac disorders | ||||
| Pericardial effusion: Tamponade | 0/84 (0%) | 0 | 2/14 (14.3%) | 3 |
| Cardiopulmonary arrest: Requiring intubation | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Fluid retention - evidence of ascites | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Diarrhea (associated with GVHD): >15ml/kg per day | 1/84 (1.2%) | 1 | 1/14 (7.1%) | 1 |
| Gastrointestinal disorders -Other, specify: pneumatosis | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Oral mucositis: Requiring intervention | 20/84 (23.8%) | 20 | 1/14 (7.1%) | 1 |
| Esophageal ulcers: Presumed viral esophagitis | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Colitis: Abdominal pain | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Pancreatitis | 3/84 (3.6%) | 3 | 0/14 (0%) | 0 |
| Oral hemorrhage: Bleeding (requiring transfusion) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| General disorders | ||||
| Fever (not neutropenic): attributed to rATG | 6/84 (7.1%) | 6 | 1/14 (7.1%) | 1 |
| Fever (not neutropenic) | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Immune system disorders | ||||
| Anaphylaxis reaction: Possible reaction to rATG | 1/84 (1.2%) | 1 | 1/14 (7.1%) | 1 |
| Infections and infestations | ||||
| Infections and infestations -Other, specify: life-threatening disseminated Adenovirus | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| nfections and infestations -Other, specify: MSSA septic shock | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Infections and infestations -Other, specify: Strep viridans, enterococcus bacteremia | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Investigations | ||||
| Elevated bilirubin (>3-10x ULN) | 2/84 (2.4%) | 2 | 2/14 (14.3%) | 2 |
| Carbon monoxide diffusing capacity decreased (DLCO) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Nervous system disorders | ||||
| Reversible posterior leukoencephalopathy syndrome (PRES) | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Seizure (conciousness altered) | 3/84 (3.6%) | 5 | 0/14 (0%) | 0 |
| Renal and urinary disorders | ||||
| Hematuria | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Acute kidney injury (reversible, requiring CRRT/dialysis) | 1/84 (1.2%) | 1 | 1/14 (7.1%) | 1 |
| Reproductive system and breast disorders | ||||
| Dysfunctional urerine (menstrual) bleeding: requiring transfusion | 1/84 (1.2%) | 1 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary hemorrhage | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| sleep apnea: Obstructive | 0/84 (0%) | 0 | 1/14 (7.1%) | 1 |
| Hypoxia: decreased O2 sat | 10/84 (11.9%) | 10 | 1/14 (7.1%) | 1 |
| Hypoxia: requiring intubation | 1/84 (1.2%) | 2 | 2/14 (14.3%) | 2 |
| Adult respiratory distress syndrome (ARDS) | 0/84 (0%) | 0 | 2/14 (14.3%) | 2 |
| Epistaxis | 2/84 (2.4%) | 2 | 0/14 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash (>50%) | 4/84 (4.8%) | 4 | 0/14 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension: requiring intervention | 3/84 (3.6%) | 3 | 0/14 (0%) | 0 |
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.
Results Point of Contact
| Name/Title | Dr. Lauri Burroughs |
|---|---|
| Organization | Fred Hutchinson Cancer Research Center |
| Phone | 206-667-2396 |
| lburroug@fredhutch.org |
Responsible Party:
Lauri Burroughs,
Associate Professor, Clinical Research Division, Fred Hutch; Director, Non-Malignant Transplant Program,
Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT00919503
Other Study ID Numbers:
- 2256.00
- NCI-2010-01277
- 2256.00
- P30CA015704
- RG2809001
First Posted:
Jun 12, 2009
Last Update Posted:
Aug 13, 2021
Last Verified:
Jul 1, 2021