Fanconi AnemiaNCT00595127
Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
A study testing Cyclophosphamide, Fludarabine and Total body irradiation (TBI) in people with Fanconi Anemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow; (2) determine if selected stem cells from the blood or… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- Cyclophosphamide, Fludarabine and Total body irradiation (TBI)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2001to May 2013
- Phase
- Interventional
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Diagnosis:
- Research participants must be have a diagnosis of Fanconi anemia (confirmed by mitomycin or diepoxybutane [DEB] chromosomal breakage testing).
- Hematologic Diagnosis and Status:
- Research participants must have one of the following hematologic diagnoses:
- Severe Aplastic Anemia (SAA)/Severe Isolated Single lineage Cytopenia
- Myelodysplastic Syndrome(MDS)
Show all 19Show fewer
- Acute leukemia.
- HLA-compatible Unrelated volunteer donors:
- Research participants who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.
- HLA-mismatched Related donors:
- Research participants who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
- The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone marrow donation. In order to undergo a Tcell depletion, a donor should be able to have a volume of 15 ml/Kg of the research participant's body weight harvested safely.
- HLA-compatible Cord Blood Units:
- Research participants who do not have a related HLA-matched donor but have an unrelated placental cord blood unit which matched at all A, B and DRB1 loci or who is mismatched at 1/6 or 2/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.
- Research participants may be of either gender or any ethnic background.
- Research participants must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%.
- At the time of referral for transplantation, research participants must be in good clinical condition without co-existing medical problems that would significantly increase the risk of the transplant procedure. Research participants must be free of infections at the time of transplant. Research participants must have a life expectancy that is greater than 8 weeks.
- Research participants must have adequate physical function measured by cardiac, Hepatic, Renal, Pulmonary.
- Research participants must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly for 5 years.
Who cannot join
- Active CNS leukemic involvement
- Female research participants who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Research participant seropositive for HIV-I/II; HTLV -I/II
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
The purpose of this research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow; (2) determine if selected stem cells from the blood or marrow can take and not cause graft-versus-host disease (GvHD), and; (3) evaluate the side effects of the combination of low dose radiation and chemotherapy drugs used for these transplants.
Read the detailed description
Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia.
If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems.
An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease.
In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to Total Body Irradiation, cyclophosphamide and fludarabine has made the chances of rejection very low.
- Conditions
- Fanconi Anemia
- Being tested
- Cyclophosphamide, Fludarabine, Total body irradiation (TBI)
- Keywords
- Fanconi, Anemia, Stem Cell, Transplant
- Medical subject headings
- Fanconi Anemia, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide (10mg/kg/day x 4days)
FludarabineDrug
Fludarabine (30mg/m^2/day x 5 days)
Total body irradiation (TBI)Radiation
TBI (450 cGY in a single fraction)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | This is an open-label single arm study of 131I-8H9, injected intravenously at 10 mCi/1.73 m^2 dose [intended specific activity of ~20 mCi/mg protein] preceded by administration of 50mg/1.73m^2 of unlabeled 8H9. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total body irradiation (TBI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence & Quality of Engraftment & Hematopoietic Reconstitution
Number of patients who engrafted
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2008 (estimated)
- Study startJun 2001
- Primary completionMay 2013
- Study completionMay 2013
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 Memorial Sloan Kettering Cancer CenterThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Miltenyi Biotec, Inc.
- Responsible party
- Sponsor
- Investigators
- Farid Boulad, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00595127
- Sponsor's protocol ID
- 01-062
- Status last verified
- Jun 2016
- First submitted
- 7 Jan 2008
- Last updated
- 10 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
- ClinicalTrials.gov ID
- NCT00595127
- Acronym / sponsor ID
- 01-062
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi, Anemia, Stem Cell, Transplant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Miltenyi Biotec, Inc.
- Study start
- Jun 2001
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 Jan 2008 (estimated)
- Results
- Posted 10 Aug 2016
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 research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow; (2) determine if selected stem cells from the blood or marrow can take and not cause graft-versus-host disease (GvHD), and; (3) evaluate the side effects of the combination of low dose radiation and chemotherapy drugs used for these transplants.
Detailed description
Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia.
If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems.
An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease.
In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to Total Body Irradiation, cyclophosphamide and fludarabine has made the chances of rejection very low.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Radiation: Total body irradiation (TBI)This is an open-label single arm study of 131I-8H9, injected intravenously at 10 mCi/1.73 m^2 dose [intended specific activity of ~20 mCi/mg protein] preceded by administration of 50mg/1.73m^2 of unlabeled 8H9. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Research participants must be have a diagnosis of Fanconi anemia (confirmed by mitomycin or diepoxybutane [DEB] chromosomal breakage testing).
- Research participants must have one of the following hematologic diagnoses:
- Research participants who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.
- Research participants who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
- The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone marrow donation. In order to undergo a Tcell depletion, a donor should be able to have a volume of 15 ml/Kg of the research participant's body weight harvested safely.
Key exclusion criteria (4 listed)
- Active CNS leukemic involvement
- Female research participants who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Research participant seropositive for HIV-I/II; HTLV -I/II
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 |
|---|---|---|
| CyclophosphamideCyclophosphamide (10mg/kg/day x 4days) | Drug | 1 |
| FludarabineFludarabine (30mg/m^2/day x 5 days) | Drug | 1 |
| Total body irradiation (TBI)TBI (450 cGY in a single fraction) | Radiation | 1 |
Primary outcome
Incidence & Quality of Engraftment & Hematopoietic Reconstitution
Time frame: 8 years
Number of patients who engrafted
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
Farid Boulad, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cyclophosphamide, Fludarabine and Total body irradiation (TBI) in people with Fanconi Anemia, run by Memorial Sloan Kettering Cancer Center 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 19 inclusion and 4 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 10 Aug 2016. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2016). 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?
Incidence & Quality of Engraftment & Hematopoietic Reconstitution (time frame: 8 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 10 Aug 2016.