Fanconi AnemiaPhase 1/2NCT00630253
Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
A Phase 1/2 study testing Anti-Thymocyte Globulin, Cyclophosphamide and Fludarabine in people with Fanconi Anemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 59 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- Anti-Thymocyte Globulin, Cyclophosphamide and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2000to 10 Oct 2020
- 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 Up to 59 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be <60 years of age with a diagnosis of Fanconi Anemia (FA).
- Patients must have an HLA-A, B, DRB1 identical sibling 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 moderately severe aplastic anemia (AA), early myelodysplastic syndrome (MDS) with no excess blasts with or without chromosomal abnormalities.
- In patients <18 years of age, moderately severe aplastic anemia is defined as having at least one of the following:
- platelet count <40 x 10^9/L
- absolute neutrophil count (ANC) <10 x 10^8/L
Show all 17Show fewer
- Hgb <9 g/dL
- In patients 18-60 years of age, moderately severe aplastic anemia is defined as having at least one of the following:
- platelet count <20 x 10^9/L
- absolute neutrophil count ANC <5 x 10^8/L
- Hgb <8 g/dL
- Early myelodysplastic syndrome, with multilineage dysplasia with < 5% blasts, with or without chromosomal anomalies.
- Adequate major organ function including:
- Cardiac: ejection fraction >45%
- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
- Karnofsky performance status >70% or Lansky >50%
- Women of child bearing age must be using adequate birth control and have a negative pregnancy test.
Who cannot join
- Active bacterial infection within one week of hematopoietic cell transplant (HCT)
- Active fungal infection at time of HCT.
- Late MDS with greater than 5% blasts in bone marrow.
- Acute myelogenous leukemia (AML) or history of AML
- Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
- Pregnant or 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: A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant and giving cyclosporine before and after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide, fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with Fanconi anemia.
Read the detailed description
OBJECTIVES:
Primary
- To determine the probability of engraftment in patients with Fanconi anemia treated with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that is T-cell depleted.
Secondary
- To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
- To evaluate the incidence of regimen-related toxicity in these patients.
- To evaluate the 1-year survival of patients treated with this regimen.
- To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma of the head and neck or cervix) in patients treated with this regimen.
OUTLINE:
- Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin IV over 4-6 hours on days -6 to -2.
- T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L.
After completion of study therapy, patients are followed periodically.
- Conditions
- Fanconi Anemia
- Being tested
- Anti-Thymocyte Globulin, Cyclophosphamide, Fludarabine, Hematopoietic Stem Cell Transplantation, Methylprednisolone
- 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
30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.
CyclophosphamideDrug
Also called Cytoxan
5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.
FludarabineDrug
Also called Fludara
35 mg/m^2 intravenously (IV) on days -6 through -2.
Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called HSCT
Bone marrow or umbilical cord blood infusion on day 0.
Also called MP
Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.
FilgrastimDrug
Also called G-CSF
5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count > or = 2.5 x 10^9/L
CyclosporineDrug
Also called CSA
Cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper.
Also called MMF
Day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours PO (to a maximum dose of 1 gram).
| Study group | Role | What they receive |
|---|---|---|
| Marrow Isolex | Experimental | bone marrow processed using Isolex 300i (for patients enrolled through April 2010) Receives: Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil |
| UCB | Experimental | No processing Notes: sibling donor UCB is used as the stem cell source and co-enroll for unlicensed UCB registry Receives: Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil |
| Marrow Clinimax | Experimental | bone marrow processed using CliniMACS (for patients enrolled beginning with the August 2010 protocol version) Receives: Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil |
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 = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
Measured: From Day 1 to event, assessed up to100 days
Secondary outcomes (4)
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
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 Overall Survival
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.
Overall survival will be defined as time from enrollment to date of death or censored at the date of last documented contact for patients still alive.
Measured: 1 Year
Number of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Measured: 1 Year
Number of Participants With Transplant Related Deaths
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation
Measured: Day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2008 (estimated)
- Study start17 Feb 2000
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margaret L. MacMillan, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00630253
- Sponsor's protocol ID
- MT2000-09
- Other IDs
- 0001M34441
- Status last verified
- Oct 2021
- First submitted
- 5 Mar 2008
- Last updated
- 12 Oct 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 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
- ClinicalTrials.gov ID
- NCT00630253
- Acronym / sponsor ID
- MT2000-09
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi anemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 17 Feb 2000 (actual)
- Primary completion
- 10 Oct 2020 (actual)
- Study completion
- 10 Oct 2020 (actual)
- First posted
- 6 Mar 2008 (estimated)
- Results
- Posted 12 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant and giving cyclosporine before and after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide, fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with Fanconi anemia.
Detailed description
OBJECTIVES:
Primary
- To determine the probability of engraftment in patients with Fanconi anemia treated with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that is T-cell depleted.
Secondary
- To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
- To evaluate the incidence of regimen-related toxicity in these patients.
- To evaluate the 1-year survival of patients treated with this regimen.
- To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma of the head and neck or cervix) in patients treated with this regimen.
OUTLINE:
- Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin IV over 4-6 hours on days -6 to -2.
- T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L.
After completion of study therapy, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Marrow Isolex | Experimental | Biological: Anti-Thymocyte Globulin, Drug: Cyclophosphamide, Drug: Fludarabine, Procedure: Hematopoietic Stem Cell Transplantation, Drug: Methylprednisolone, Drug: Filgrastim, Drug: Cyclosporine, Drug: Mycophenolate Mofetilbone marrow processed using Isolex 300i (for patients enrolled through April 2010) |
| UCB | Experimental | Biological: Anti-Thymocyte Globulin, Drug: Cyclophosphamide, Drug: Fludarabine, Procedure: Hematopoietic Stem Cell Transplantation, Drug: Methylprednisolone, Drug: Filgrastim, Drug: Cyclosporine, Drug: Mycophenolate MofetilNo processing Notes: sibling donor UCB is used as the stem cell source and co-enroll for unlicensed UCB registry |
| Marrow Clinimax | Experimental | Biological: Anti-Thymocyte Globulin, Drug: Cyclophosphamide, Drug: Fludarabine, Procedure: Hematopoietic Stem Cell Transplantation, Drug: Methylprednisolone, Drug: Filgrastim, Drug: Cyclosporine, Drug: Mycophenolate Mofetilbone marrow processed using CliniMACS (for patients enrolled beginning with the August 2010 protocol version) |
Who may qualify
- Ages
- Up to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- Patients must be <60 years of age with a diagnosis of Fanconi Anemia (FA).
- Patients must have an HLA-A, B, DRB1 identical sibling 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 moderately severe aplastic anemia (AA), early myelodysplastic syndrome (MDS) with no excess blasts with or without chromosomal abnormalities.
- 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 (6 listed)
- Active bacterial infection within one week of hematopoietic cell transplant (HCT)
- Active fungal infection at time of HCT.
- Late MDS with greater than 5% blasts in bone marrow.
- Acute myelogenous leukemia (AML) or history of AML
- Malignant solid tumor (e.g. 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 |
|---|---|---|
| Anti-Thymocyte GlobulinAlso: ATG30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2. | Biological | Marrow Clinimax, Marrow Isolex, UCB |
| CyclophosphamideAlso: Cytoxan5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3. | Drug | Marrow Clinimax, Marrow Isolex, UCB |
| FludarabineAlso: Fludara35 mg/m^2 intravenously (IV) on days -6 through -2. | Drug | Marrow Clinimax, Marrow Isolex, UCB |
| Hematopoietic Stem Cell TransplantationAlso: HSCTBone marrow or umbilical cord blood infusion on day 0. | Procedure or surgery | Marrow Clinimax, Marrow Isolex, UCB |
| MethylprednisoloneAlso: MPMethylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG. | Drug | Marrow Clinimax, Marrow Isolex, UCB |
| FilgrastimAlso: G-CSF5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count > or = 2.5 x 10^9/L | Drug | Marrow Clinimax, Marrow Isolex, UCB |
| CyclosporineAlso: CSACyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper. | Drug | Marrow Clinimax, Marrow Isolex, UCB |
| Mycophenolate MofetilAlso: MMFDay -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours PO (to a maximum dose of 1 gram). | Drug | Marrow Clinimax, Marrow Isolex, UCB |
Primary outcome
Number of Participants Experiencing Graft Failure
Time frame: From Day 1 to event, assessed up to100 days
graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
4 secondary outcomes
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Time frame: Day 42
Number of Participants Experiencing Overall Survival
Time frame: 1 Year
Number of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Time frame: 1 Year
Number of Participants With Transplant Related Deaths
Time frame: Day 100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 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 L. 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 Anti-Thymocyte Globulin, Cyclophosphamide and Fludarabine 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 17 inclusion and 6 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 12 Oct 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 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 12 Oct 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?
Number of Participants Experiencing Graft Failure (time frame: From Day 1 to event, assessed up to100 days). 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 12 Oct 2021.