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Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders

Primary Purpose

Non-Neoplastic Hematologic and Lymphocytic Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Bone Marrow Transplantation
Anti-Thymocyte Globulin
Cyclosporine
Fludarabine Phosphate
Laboratory Biomarker Analysis
Methotrexate
Mycophenolate Mofetil
Peripheral Blood Stem Cell Transplantation
Tacrolimus
Total-Body Irradiation
Treosulfan
Umbilical Cord Blood Transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Neoplastic Hematologic and Lymphocytic Disorder focused on measuring nonmalignant diseases, nonmalignant inherited disorders, primary immunodeficiency diseases, primary immune deficiency disorders, chronic granulomatous, disease, IPEX syndrome, hemophagocytic lymphohistiocytosis, Wiskott Aldrich Syndrome, bone marrow failure syndromes, Shwachman Diamond Syndrome, Dyskeratosis Congenita, Diamond Blackfan Anemia, inborn errors of metabolism, metabolic diseases, hemoglobinopathies, sickle cell disease, thalassemia, reduced intensity transplantation, hematopoietic cell transplantation, bone marrow transplantation, umbilical cord blood transplantation

Eligibility Criteria

undefined - 49 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Colorado
  • Oregon Health and Science University
  • Vanderbilt University/Ingram Cancer Center
  • Seattle Children's Hospital
  • Fred Hutch/University of Washington Cancer Consortium
  • Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Regimen A (PBSCT and BMT)

Regimen B (UBCT)

Arm 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.

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.

Outcomes

Primary Outcome Measures

Preliminary Efficacy
Number of patients engrafted (>5% donor CD3+ peripheral blood chimerisms) at 1 year following transplant

Secondary Outcome Measures

Non-relapse Mortality
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
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
Number of patients diagnosed with chronic GVHD and requiring systemic immunosuppression within 1 year following transplant
Donor Chimerism CD3 at 100 Days 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
Number of patients with no evidence of disease at one year following transplant
Immune Reconstitution Following Hematopoietic Cell Transplantation
Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant
Number of Participants With Infections
Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant
Overall Survival
Number of patients alive at 1 year following transplant
Donor Chimerism CD33 at Day 100 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.

Full Information

First Posted
June 11, 2009
Last Updated
July 21, 2021
Sponsor
Fred Hutchinson Cancer Center
Collaborators
medac GmbH, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00919503
Brief Title
Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders
Official Title
Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
July 31, 2009 (Actual)
Primary Completion Date
June 10, 2020 (Actual)
Study Completion Date
June 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
medac GmbH, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Neoplastic Hematologic and Lymphocytic Disorder
Keywords
nonmalignant diseases, nonmalignant inherited disorders, primary immunodeficiency diseases, primary immune deficiency disorders, chronic granulomatous, disease, IPEX syndrome, hemophagocytic lymphohistiocytosis, Wiskott Aldrich Syndrome, bone marrow failure syndromes, Shwachman Diamond Syndrome, Dyskeratosis Congenita, Diamond Blackfan Anemia, inborn errors of metabolism, metabolic diseases, hemoglobinopathies, sickle cell disease, thalassemia, reduced intensity transplantation, hematopoietic cell transplantation, bone marrow transplantation, umbilical cord blood transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regimen A (PBSCT and BMT)
Arm Type
Experimental
Arm 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.
Arm Title
Regimen B (UBCT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Bone Marrow Transplantation
Other Intervention Name(s)
Allo BMT, Allogeneic BMT
Intervention Description
Infused IV
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya
Intervention Description
Given IV or PO
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given IV or PO
Intervention Type
Procedure
Intervention Name(s)
Peripheral Blood Stem Cell Transplantation
Other Intervention Name(s)
PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation
Intervention Description
Infused IV
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given IV or PO
Intervention Type
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
Total Body Irradiation, Whole-Body Irradiation
Intervention Description
Undergo total body irradiation
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Treosulphan, Tresulfon
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Umbilical Cord Blood Transplantation
Other Intervention Name(s)
Cord Blood Transplantation, UCB transplantation
Intervention Description
Single or double unit umbilical cord blood transplant, infused IV
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
Title
Non-relapse Mortality
Description
Number of patients who experienced non-relapse mortality by 1 year following transplant
Time Frame
1 year following transplant
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
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
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
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
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
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
Title
Overall Survival
Description
Number of patients alive at 1 year following transplant
Time Frame
1 year following transplant
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lauri M. Burroughs
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders

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