AzTrials
AzTrials

Non-Neoplastic Hematologic and Lymphocytic DisorderPhase 2NCT00919503

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

A Phase 2 study testing Allogeneic Bone Marrow Transplantation, Anti-Thymocyte Globulin and Cyclosporine in people with Non-Neoplastic Hematologic and Lymphocytic Disorder, run by Fred Hutchinson Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 49 years
What is being tested?
Allogeneic Bone Marrow Transplantation, Anti-Thymocyte Globulin and Cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
6 sitesUnited States
Study dates
31 Jul 2009to 10 Jun 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 49 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen

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.

Read the 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.

Being tested
Allogeneic Bone Marrow Transplantation, Anti-Thymocyte Globulin, Cyclosporine, Fludarabine Phosphate, Laboratory Biomarker Analysis
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
Medical subject headings
Primary Immunodeficiency Diseases, Disease, Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome, Lymphohistiocytosis, Hemophagocytic, Wiskott-Aldrich Syndrome, Bone Marrow Failure Disorders, Shwachman-Diamond Syndrome, Dyskeratosis Congenita

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Infused IV

  • Anti-Thymocyte GlobulinBiological

    Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given IV or PO

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support

    Infused IV

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation

    Undergo total body irradiation

  • TreosulfanDrug

    Also called 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Treosulphan

    Given IV

  • Umbilical Cord Blood TransplantationProcedure or surgery

    Also called Cord Blood Transplantation, UCB transplantation

    Single or double unit umbilical cord blood transplant, infused IV

Study groups in NCT00919503
Study groupRoleWhat they receive
Regimen A (PBSCT and BMT)ExperimentalCONDITIONING 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.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Drug: Treosulfan
Regimen B (UBCT)ExperimentalCONDITIONING 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.
Receives: Biological: Anti-Thymocyte Globulin; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Drug: Treosulfan; Procedure: Umbilical Cord Blood Transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Preliminary Efficacy

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

    Measured: 1 year following transplant

Secondary outcomes (9)

  1. Non-relapse Mortality

    Number of patients who experienced non-relapse mortality by 1 year following transplant

    Measured: 1 year following transplant

  2. 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

    Measured: Day 100 post transplant

  3. 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

    Measured: 1 year following transplant

  4. 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.

    Measured: Day 100 post transplant

  5. Disease Response at One Year Following Hematopoietic Cell Transplantation

    Number of patients with no evidence of disease at one year following transplant

    Measured: 1 year following transplant

  6. Immune Reconstitution Following Hematopoietic Cell Transplantation

    Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant

    Measured: 1 year following transplant

  7. Number of Participants With Infections

    Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant

    Measured: 100 days post transplant

  8. Overall Survival

    Number of patients alive at 1 year following transplant

    Measured: 1 year following transplant

  9. 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.

    Measured: 100 days post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2009 (estimated)
  2. Study start31 Jul 2009
  3. Primary completion10 Jun 2020
  4. Study completion10 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00919503
Sponsor's protocol ID
2256.00
Other IDs
NCI-2010-01277, 2256.00, P30CA015704, RG2809001
Status last verified
Jul 2021
First submitted
11 Jun 2009
Last updated
13 Aug 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Bone Marrow Transplantation, Anti-Thymocyte Globulin and Cyclosporine in people with Non-Neoplastic Hematologic and Lymphocytic Disorder, run by Fred Hutchinson Cancer Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Preliminary Efficacy (time frame: 1 year following transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00919503.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in