Fanconi AnemiaPhase 1/2NCT00167206
Stem Cell Transplantation for Fanconi Anemia
A Phase 1/2 study testing Hematopoietic Stem Cell Transplant, Thymic Shielding During Radiation and Total Body Irradiation in people with Fanconi Anemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- Hematopoietic Stem Cell Transplant, Thymic Shielding During Radiation and Total Body Irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Dec 2008
- Phase
- Phase 1/2
- 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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
- Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
- Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.
- Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
- Platelet count <20 x 10^9/L
- ANC <5 x 10^8/L
Show all 14Show fewer
- Hgb <8 g/dL
- Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
- High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
- Adequate major organ function including
- Cardiac: ejection fraction greater than (>)45%
- Hepatic: bilirubin, AST/ALT, ALP <2 x normal
- Karnofsky performance status >70% or Lansky performance status >50%
- Women of child-bearing age must be using adequate birth control and have a negative pregnancy test
Who cannot join
- Available HLA-genotypically identical related donor
- History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
- Refractory anemia with excess blasts, or leukemia
- Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
- History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
- Pregnant or lactating female
- Prior radiation therapy preventing use of total body irradiation (TBI) 450 centigray (cGy)
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia
The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.
Read the detailed description
All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.
- Conditions
- Fanconi Anemia
- Being tested
- Hematopoietic Stem Cell Transplant, Thymic Shielding During Radiation, Total Body Irradiation, Cyclophosphamide, Fludarabine
- Keywords
- Stem Cell Transplant, Thymic Shielding, Total Body Irradiation, Chemotherapy
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Stem Cell TransplantProcedure or surgery
Also called Bone Marrow Transplant
Bone marrow failure may be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.
Thymic Shielding During RadiationProcedure or surgery
Also called TBI
protecting the thymus during total body radiation (450 cGy administered)
Total Body IrradiationProcedure or surgery
Also called Radiation Therapy, Therapuetic Radiation
Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.
Cyclophosphamide, FludarabineDrug
Also called Cytoxan, Fludara
Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line
| Study group | Role | What they receive |
|---|---|---|
| HSCT Patients | Experimental | Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT) Receives: Procedure: Hematopoietic Stem Cell Transplant; Procedure: Thymic Shielding During Radiation; Procedure: Total Body Irradiation; Drug: Cyclophosphamide, Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
Calculated from Day 1 of hematopoietic cell transplant to Day 42 post-transplant. Hematopoietic recovery and engraftment is defined as the first of three consecutive days the patient's absolute neutrophil count is greater than or equal to 0.5X10^9/Liter.
Measured: Day 42 after hematopoietic cell transplant
Secondary outcomes (8)
Number of Patients Who Exhibited Secondary Graft Failure
Calculated from Day 1 of hematopoietic cell transplant to Day 100 after transplant. A complication after Bone Marrow Transplant in which the transplanted stem cells do not grow in the recipient's bone marrow and thus do not produce new blood cells.
Measured: Day 100 after hematopoietic cell transplant
Number of Patients With Acute Graft Versus-Host Disease (aGVHD)
Calculated from Day 1 of hematopoietic cell transplant to Day 100 after transplant. GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Measured: Day 100 after hematopoietic cell transplant
Number of Patients With Chronic Graft Versus-Host Disease (GVHD)
Calculated from Day 1 of hematopoietic cell transplant to 1 year after transplant. GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Measured: 1 year after hematopoietic cell transplant
Number of Patients Who Exhibited Regimen-related Toxicity (RRT)
Calculated from Day 1 of hematopoietic cell transplant to 1 year after transplant. Regimen-related toxicity involves harmful effects in an organism through exposure to the treatment given.
Measured: 1 year after hematopoietic cell transplant
Immune Reconstitution - Mean Value (1 Year)
Calculated mean value of patient CD4 values collected at intervals from Day 30 through 1 year post-transplant.
Measured: 1 year post-transplant.
Immune Reconstitution - Mean Value (2 Years)
Calculated mean value of patient CD4 values collected at intervals from Day 30 through 2 years post-transplant.
Measured: at 2 years after transplant
Number of Patients Alive at 1 Year
Calculated from Day 1 of hematopoietic cell transplant to 1 year post-transplant.
Measured: 1 year after transplant
Number of Patients Alive at 2 Years
Calculated from Day 1 of hematopoietic cell transplant to 2 years post-transplant.
Measured: 2 years after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startMar 2004
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: Treatment with thymic shielding found safe, another study started.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margaret MacMillan, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167206
- Sponsor's protocol ID
- 0312M54991
- Other IDs
- MT2003-18
- Status last verified
- Aug 2019
- First submitted
- 9 Sep 2005
- Last updated
- 26 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.
PubMed 25824692
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia
- ClinicalTrials.gov ID
- NCT00167206
- Acronym / sponsor ID
- 0312M54991
- Conditions
- Fanconi Anemia
- Keywords
- Stem Cell Transplant, Thymic Shielding, Total Body Irradiation, Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Treatment with thymic shielding found safe, another study started.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Mar 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Posted 26 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.
Detailed description
All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSCT Patients | Experimental | Procedure: Hematopoietic Stem Cell Transplant, Procedure: Thymic Shielding During Radiation, Procedure: Total Body Irradiation, Drug: Cyclophosphamide, FludarabinePatients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT) |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
- Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
- Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.
- Adequate major organ function including
- Women of child-bearing age must be using adequate birth control and have a negative pregnancy test
Key exclusion criteria (7 listed)
- Available HLA-genotypically identical related donor
- History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
- Refractory anemia with excess blasts, or leukemia
- Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
- History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
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 |
|---|---|---|
| Hematopoietic Stem Cell TransplantAlso: Bone Marrow TransplantBone marrow failure may be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover. | Procedure or surgery | HSCT Patients |
| Thymic Shielding During RadiationAlso: TBIprotecting the thymus during total body radiation (450 cGy administered) | Procedure or surgery | HSCT Patients |
| Total Body IrradiationAlso: Radiation Therapy, Therapuetic RadiationSix days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus. | Procedure or surgery | HSCT Patients |
| Cyclophosphamide, FludarabineAlso: Cytoxan, FludaraDay -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line | Drug | HSCT Patients |
Primary outcome
Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
Time frame: Day 42 after hematopoietic cell transplant
Calculated from Day 1 of hematopoietic cell transplant to Day 42 post-transplant. Hematopoietic recovery and engraftment is defined as the first of three consecutive days the patient's absolute neutrophil count is greater than or equal to 0.5X10^9/Liter.
8 secondary outcomes
Number of Patients Who Exhibited Secondary Graft Failure
Time frame: Day 100 after hematopoietic cell transplant
Number of Patients With Acute Graft Versus-Host Disease (aGVHD)
Time frame: Day 100 after hematopoietic cell transplant
Number of Patients With Chronic Graft Versus-Host Disease (GVHD)
Time frame: 1 year after hematopoietic cell transplant
Number of Patients Who Exhibited Regimen-related Toxicity (RRT)
Time frame: 1 year after hematopoietic cell transplant
Immune Reconstitution - Mean Value (1 Year)
Time frame: 1 year post-transplant.
Immune Reconstitution - Mean Value (2 Years)
Time frame: at 2 years after transplant
Number of Patients Alive at 1 Year
Time frame: 1 year after transplant
Number of Patients Alive at 2 Years
Time frame: 2 years after transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25824692MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.
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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.
Margaret MacMillan, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hematopoietic Stem Cell Transplant, Thymic Shielding During Radiation and Total Body Irradiation in people with Fanconi Anemia, 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 14 inclusion and 7 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: stopped early, as of the sponsor's last update on 26 Aug 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 26 Nov 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 Who Exhibited Hematopoietic Recovery and Engraftment (time frame: Day 42 after hematopoietic cell 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 NCT00167206, which also lists 1 linked publication.
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 26 Aug 2019.