Fanconi AnemiaPhase 2NCT00258427
Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
A Phase 2 study testing anti-thymocyte globulin, filgrastim and busulfan in people with Fanconi Anemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. Read more about this study
- Who is it for?
- Ages Up to 44 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- anti-thymocyte globulin, filgrastim and busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2002to 10 Oct 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 44 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be <45 years of age with a diagnosis of Fanconi anemia with:
- Biallelic BRCA2 mutations, or
- Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count <20 * 10^9, - absolute neutrophil count (ANC) <5 * 10^8/L, - Hgb <8 g/dL
- Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.
- Adequate major organ function including:
- Cardiac: ejection fraction >45%
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- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis)
- Karnofsky performance status >70% or Lansky >50%
- Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.
Who cannot join
- Active CNS leukemia at time of HSCT.
- Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).
- Pregnant or lactating female.
- Donor Inclusion Criteria:
- Donor must be in good health based on review of systems and results of physical examination.
- Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.
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- HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
- Female donors of childbearing potential must have a negative pregnancy test.
- Unrelated donors must agree to peripheral blood stem cell (PBSC) donation
- Donor Exclusion Criteria:
- Donor is a lactating female.
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: Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia.
PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.
Read the detailed description
OBJECTIVES:
Primary
- Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the tolerability of mycophenolate mofetil in these patients.
- Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
- Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
- Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
- Determine the probability of 1-year survival of patients treated with this regimen.
OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other).
- Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.
- Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.
- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45.
- Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
After completion of study treatment, patients are followed periodically for 3 years.
- Conditions
- Fanconi Anemia
- Being tested
- anti-thymocyte globulin, filgrastim, busulfan, cyclophosphamide, fludarabine phosphate
- Keywords
- Fanconi anemia
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
Also called ATG
Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.
filgrastimBiological
Also called G-CSF
given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L)
busulfanDrug
Also called Busulfex
Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old)
cyclophosphamideDrug
Also called Cytoxan
10 mg/kg intravenously (IV) on Days -5 through -2.
Also called Fludara
35 mg/m^2 intravenously (IV) on Days -5 through -2.
Also called Medrol
1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.
Hematopoietic stem cell transplantationBiological
Also called HSCT
Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.
| Study group | Role | What they receive |
|---|---|---|
| Marrow Isolex | Experimental | Bone marrow processed using Isolex300i Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation |
| USB arm | Experimental | No processing Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation |
| Marrow Clinimacs | Experimental | Bone marrow processed using CliniMACS system Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation |
| Sibling without CliniMacs | Experimental | Sibling donor without the use of CliniMACS system Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Graft Failure
Graft failure is defined as absolute neutrophil count( ANC ) <5 x 10^8/L by day 30.
Measured: Day 30
Secondary outcomes (7)
Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.
Measured: Day 42
Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.
Measured: 1 year
Number of Participants Experiencing Acute Graft-Versus-Host Disease
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Measured: 1 year
Number of Participants Experiencing Acute Graft-Versus-Host Disease
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Measured: Day 42
Number of Participants Experiencing Relapse
Patients with leukemia will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate.
Measured: 1 Year
Number of Participants Experiencing Overall Survival
Overall Survival - Number of patients alive at 1 year post transplant
Measured: 1 Year
Number of Participants Experiencing Major Infections
Number of participants experiencing Major Infections by the end of treatment
Measured: Day 1 through 1 year post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2005 (estimated)
- Study start26 Mar 2002
- Primary completion10 Oct 2020
- Study completion10 Oct 2020
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 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 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
- NCT00258427
- Sponsor's protocol ID
- 2002LS014
- Other IDs
- MT2002-02, 0202M18741
- Status last verified
- Nov 2021
- First submitted
- 22 Nov 2005
- Last updated
- 2 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
- ClinicalTrials.gov ID
- NCT00258427
- Acronym / sponsor ID
- 2002LS014
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 26 Mar 2002 (actual)
- Primary completion
- 10 Oct 2020 (actual)
- Study completion
- 10 Oct 2020 (actual)
- First posted
- 24 Nov 2005 (estimated)
- Results
- Posted 23 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia.
PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.
Detailed description
OBJECTIVES:
Primary
- Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the tolerability of mycophenolate mofetil in these patients.
- Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
- Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
- Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
- Determine the probability of 1-year survival of patients treated with this regimen.
OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other).
- Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.
- Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.
- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45.
- Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
After completion of study treatment, patients are followed periodically for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Marrow Isolex | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: methylprednisolone, Biological: Hematopoietic stem cell transplantationBone marrow processed using Isolex300i |
| USB arm | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: methylprednisolone, Biological: Hematopoietic stem cell transplantationNo processing |
| Marrow Clinimacs | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: methylprednisolone, Biological: Hematopoietic stem cell transplantationBone marrow processed using CliniMACS system |
| Sibling without CliniMacs | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: methylprednisolone, Biological: Hematopoietic stem cell transplantationSibling donor without the use of CliniMACS system |
Who may qualify
- Ages
- Up to 44 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Patients must be <45 years of age with a diagnosis of Fanconi anemia with:
- Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.
- Adequate major organ function including:
- Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.
Key exclusion criteria (11 listed)
- Active CNS leukemia at time of HSCT.
- Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).
- Pregnant or lactating female.
- Donor must be in good health based on review of systems and results of physical examination.
- Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.
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 |
|---|---|---|
| anti-thymocyte globulinAlso: ATGGiven 15 mg/kg/day intravenously every 12 hours on Days -5 through -1. | Biological | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| filgrastimAlso: G-CSFgiven 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L) | Biological | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| busulfanAlso: BusulfexBusulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old) | Drug | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| cyclophosphamideAlso: Cytoxan10 mg/kg intravenously (IV) on Days -5 through -2. | Drug | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| fludarabine phosphateAlso: Fludara35 mg/m^2 intravenously (IV) on Days -5 through -2. | Drug | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| methylprednisoloneAlso: Medrol1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1. | Drug | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
| Hematopoietic stem cell transplantationAlso: HSCTInfused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program. | Biological | Marrow Clinimacs, Marrow Isolex, Sibling without CliniMacs, USB arm |
Primary outcome
Number of Participants Experiencing Graft Failure
Time frame: Day 30
Graft failure is defined as absolute neutrophil count( ANC ) <5 x 10^8/L by day 30.
7 secondary outcomes
Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Time frame: Day 42
Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Time frame: 1 year
Number of Participants Experiencing Acute Graft-Versus-Host Disease
Time frame: 1 year
Number of Participants Experiencing Acute Graft-Versus-Host Disease
Time frame: Day 42
Number of Participants Experiencing Relapse
Time frame: 1 Year
Number of Participants Experiencing Overall Survival
Time frame: 1 Year
Number of Participants Experiencing Major Infections
Time frame: Day 1 through 1 year post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2021.
- 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.
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 2 study testing anti-thymocyte globulin, filgrastim and busulfan 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 9 inclusion and 11 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 2 Dec 2021. 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 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 23 Mar 2011). 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 Participants Experiencing Graft Failure (time frame: Day 30). 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 2 Dec 2021.