Diamond-Blackfan AnemiaPhase 2/3NCT00176878
Stem Cell Transplant for Bone Marrow Failure Syndromes
A Phase 2/3 study testing Stem cell transplant, Fludarabine monophosphate and Total lymphoid irradiation in people with Diamond-Blackfan Anemia and Kostmann's Neutropenia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders. Read more about this study
- Who is it for?
- Ages Up to 35 years
- Conditions the study is for
- Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome
- What is being tested?
- Stem cell transplant, Fludarabine monophosphate and Total lymphoid irradiation
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2000to Mar 2009
- Phase
- Phase 2/3
- 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 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients eligible for transplantation under this protocol will be <35 years of age, and will be diagnosed with:
- a bone marrow failure syndrome unresponsive to available therapy, including but not limited to Diamond-Blackfan anemia, Shwachman Diamond syndrome or Kostmann's neutropenia but exclusive of aplastic anemia.
- Diamond Blackfan Anemia:
- Patients must show evidence of steroid resistance requiring equivalent of >6 transfusions yearly despite steroid therapy.
- Evidence of developing aplasia or myelodysplasia will also be criteria for transplantation.
- Kostmann's Neutropenia, Shwachman-Diamond syndrome:
- Patients must have been previously diagnosed as having a clinical picture characteristic of Shwachman-Diamond syndrome (exocrine pancreatic insufficiency, growth retardation, metaphyseal dysostosis, neutropenia), or must have a bone marrow aspirate consistent with Kostmann's neutropenia, with no evidence of acute leukemia.
- Patients must have failed therapy with granulocyte-colony stimulating factor (G-CSF), as determined by an inability to maintain an absolute neutrophil count (ANC) >750 cells/ml(3), or manifesting recurrent infections despite G-CSF administration resulting in life threatening infections or repeated hospitalizations (<4 /year).
Who cannot join
- Patients >35 years of age
- Karnofsky score <70%
- Hepatic dysfunction as determined by bilirubin >3.0, ALT >150, or active hepatitis
- Pulmonary function tests with forced volume vital capacity (FVC) and forced expiratory volume (FEV) <70%; O2 saturation <94%
- Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
- Cardiac compromise, with left ejection fraction <45%.
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- Severe, stable neurologic impairment.
- Human immunodeficiency virus (HIV) positivity.
- Pregnant or lactating females
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
About this study
Official title: Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.
Read the detailed description
Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.
Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).
Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.
- Being tested
- Stem cell transplant, Fludarabine monophosphate, Total lymphoid irradiation, Busulfan, anti-thymocyte globulin
- Keywords
- Stem cell transplant, T-cell depletion, TLI, bone marrow failure disorders
- Medical subject headings
- Anemia, Diamond-Blackfan, Shwachman-Diamond Syndrome, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem cell transplantProcedure or surgery
Also called BMT
Stem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10^9/kg.
Fludarabine monophosphateDrug
Also called Fludara
fludarabine 175 mg/m^2 (total) on Days -6 through -3.
Total lymphoid irradiationProcedure or surgery
Also called TLI
Dose 500 cGy radiation therapy to specific areas of the body
BusulfanDrug
Also called Busulfex
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),
anti-thymocyte globulinBiological
Also called ATG
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter
| Study group | Role | What they receive |
|---|---|---|
| Bone Marrow Failure Disorders | Experimental | Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome Receives: Procedure: Stem cell transplant; Drug: Fludarabine monophosphate; Procedure: Total lymphoid irradiation; Drug: Busulfan; Biological: anti-thymocyte globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Alive (Survival) at 2 Years
Calculated from day 1 of transplant to last contact.
Measured: 2 years
Secondary outcomes (5)
Number of Patients Alive at Three Years (Survival)
Number of subjects who survived 3 years post-transplant.
Measured: 3 years
Number of Patients With Succcessful Engraftment After Transplantation
Number of patients who received non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen and exhibited engraftment at Day 42.
Measured: 42 Days
Number of Patients With Grade 2-4 Acute Graft Versus Host Disease
Number of patients with Grade 2, 3 and 4 Acute (normally observed within the first 100 days) Graft Versus Host Disease. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening.
Measured: 100 Days
Number of Patients With Chronic Graft Versus Host Disease
Number of patients who exhibited chronic (normally occurs after 100 days) Graft Versus Host Disease at 2 years post transplant. Chronic graft-versus-host-disease, over its long-term course, can also cause damage to the connective tissue and exocrine glands.
Measured: 2 years
Number of Patients With Disease Recurrence
Number of patients who exhibited disease recurrence at 2 years.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJun 2000
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diamond-Blackfan AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Orchard, MD, Principal investigator, University of Minnesota Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00176878
- Sponsor's protocol ID
- MT2000-18
- Other IDs
- 9504M09637
- Status last verified
- Dec 2017
- First submitted
- 12 Sep 2005
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders
- ClinicalTrials.gov ID
- NCT00176878
- Acronym / sponsor ID
- MT2000-18
- Keywords
- Stem cell transplant, T-cell depletion, TLI, bone marrow failure disorders
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jun 2000
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 6 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.
Detailed description
Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.
Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).
Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bone Marrow Failure Disorders | Experimental | Procedure: Stem cell transplant, Drug: Fludarabine monophosphate, Procedure: Total lymphoid irradiation, Drug: Busulfan, Biological: anti-thymocyte globulinPatients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome |
Who may qualify
- Ages
- Up to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Patients eligible for transplantation under this protocol will be <35 years of age, and will be diagnosed with:
- Diamond Blackfan Anemia:
- Kostmann's Neutropenia, Shwachman-Diamond syndrome:
Key exclusion criteria (9 listed)
- Patients >35 years of age
- Karnofsky score <70%
- Hepatic dysfunction as determined by bilirubin >3.0, ALT >150, or active hepatitis
- Pulmonary function tests with forced volume vital capacity (FVC) and forced expiratory volume (FEV) <70%; O2 saturation <94%
- Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem cell transplantAlso: BMTStem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10^9/kg. | Procedure or surgery | Bone Marrow Failure Disorders |
| Fludarabine monophosphateAlso: Fludarafludarabine 175 mg/m^2 (total) on Days -6 through -3. | Drug | Bone Marrow Failure Disorders |
| Total lymphoid irradiationAlso: TLIDose 500 cGy radiation therapy to specific areas of the body | Procedure or surgery | Bone Marrow Failure Disorders |
| BusulfanAlso: BusulfexBusulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter), | Drug | Bone Marrow Failure Disorders |
| anti-thymocyte globulinAlso: ATGanti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter | Biological | Bone Marrow Failure Disorders |
Primary outcome
Number of Patients Alive (Survival) at 2 Years
Time frame: 2 years
Calculated from day 1 of transplant to last contact.
5 secondary outcomes
Number of Patients Alive at Three Years (Survival)
Time frame: 3 years
Number of Patients With Succcessful Engraftment After Transplantation
Time frame: 42 Days
Number of Patients With Grade 2-4 Acute Graft Versus Host Disease
Time frame: 100 Days
Number of Patients With Chronic Graft Versus Host Disease
Time frame: 2 years
Number of Patients With Disease Recurrence
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Orchard, MD principal investigator
University of Minnesota Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Stem cell transplant, Fludarabine monophosphate and Total lymphoid irradiation in people with Diamond-Blackfan Anemia and Kostmann's Neutropenia, run by Masonic Cancer Center, University of Minnesota at 1 site 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 8 inclusion and 9 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 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 6 Aug 2009). 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?
Number of Patients Alive (Survival) at 2 Years (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2017.