Fanconi AnemiaEarly Phase 1NCT00965666
Pilot Study of Etanercept (Enbrel) in Children With Fanconi Anemia
A Early Phase 1 study testing Etanercept in people with Fanconi Anemia, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The purpose of this research study is to evaluate the safety of the drug Etanercept (Enbrel) and to determine if this drug can help in the treatment of early bone marrow failure in patients with Fanconi anemia. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- Etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Oct 2010
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a diagnosis of FA proven by a DEB test conducted in the cytogenetics lab of Dr. Arleen Auerbach, Rockefeller University Hospital.
- Patients must have evidence of early marrow failure i.e. reduction in at least one cell line on two separate occasions at least one month apart e.g. platelet count of < 100,000 per cubic millimeter, hemoglobin < 9 gm/dl and/or absolute neutrophil count (ANC) of < 1000
- Negative pregnancy test (conducted via serum β-HCG screen) - done before the first dose of study drug in all women (except those surgically sterile, at least 5 years postmenopausal, or under the age of 10 years)
- Sexually active patients of childbearing potential must agree to use medically acceptable form of contraception during screening and throughout the study
- Patients or designees must have the ability to self-inject investigational product or have a care giver at home who can administer subcutaneous injections
- Patients or designees must be able and willing to give written informed consent and comply with the requirements of the study protocol and must authorize release and use of protected health information
- Patients must have a negative TB skin test at entry into the study
Who cannot join
- Patients < 4 yrs of age
- Patients with advanced marrow failure i.e. transfusion dependent, will not be eligible as we anticipate that stem cell depletion will already be advanced at this stage.
- Patients currently enrolled in another investigational device or drug trial(s) (defined as a drug not approved by the FDA), or who have received other investigational agent(s) within 28 days of baseline visit with the exception of CCHMC IRB protocol # 03-9-11, "Thyroid Hormone in Children with Fanconi Anemia"
- Patients on androgen therapy
- Patients who have received immunosuppressive agents within the last 3 months prior to enrollment
- Patients who have any grade 3 or 4 adverse event or laboratory toxicity other than in Blood or Bone Marrow (as per the NCI CTC criteria) at the time of the screening visit or at any time during the study, that in the opinion of the Investigator would preclude participation in the study
Show all 22Show fewer
- Patients with active infections within 4 weeks before the screening/baseline visit
- Patients with untreated Lyme disease
- Patients with a recent or past history of fungal infection
- Patients who have history of TB or TB exposure, chronic hepatitis B or hepatitis C, SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy
- Patients with known hypersensitivity to Etanercept (Enbrel) or any of its components or who are known to have antibodies to Etanercept (Enbrel).
- Patients who have received hematopoietic growth factor for greater than 3 consecutive days in the 6 months before study enrollment (i.e., erythropoietin, filgrastim, neupogen, sargramostin) for clinical purposes to improve bone marrow function. Patients receiving hematopoietic growth factor for stem cell mobilization and collection only are not excluded from this study.
- Patients with an available matched sibling donor and clinically indicated need for bone marrow transplant
- Patients with renal failure requiring dialysis
- Patients with a total bilirubin >3 mg/dl and/or SGPT >200 at time of enrollment
- Patients who are pregnant or breastfeeding or are a female at risk of pregnancy and are unable to practice safe sex during the length of the study
- Patients who are HIV positive
- Patients with severe co-morbidities (diabetes mellitus requiring insulin, CHF of any severity, MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, uncontrolled hypertension, oxygen-dependent severe pulmonary disease, history of cancer within 5 years (other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer)
- Patients who have any mycobacterial disease or known history of any other immuno-suppressing disease
- Patients with a history of recent alcohol or substance abuse (< 1 year)
- Patients with a history of non-compliance with other therapies
- Patients who have any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
About this study
Official title: Etanercept (Enbrel) in Children With Fanconi Anemia and Early Bone Marrow Failure: A Pilot Study
The purpose of this research study is to evaluate the safety of the drug Etanercept (Enbrel) and to determine if this drug can help in the treatment of early bone marrow failure in patients with Fanconi anemia.
Read the detailed description
Patients with FA are treated with blood products (transfusions), injections to stimulate white blood cell production, and/or androgen therapy once they reach advanced stages of bone marrow failure. Although these therapies lead to temporary improvement in the blood counts, they are associated with potential serious side effects. Currently, the only known potential cure for bone marrow failure in Fanconi Anemia is a stem cell transplant, which is usually done at the late stages of bone marrow failure and is again associated with significant toxicity.
Studies show that patients with FA are very sensitive to and produce unusually high levels of a protein called tumor necrosis factor alpha (TNF-α) that causes bone marrow cells to die. We will study whether a drug called Etanercept that reduces levels of TNF-α will delay or prevent the progressive bone marrow failure associated with FA. Etanercept has been successfully used in children with arthritis.
Primary Objectives:
- To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure.
- To assess efficacy of Etanercept (Enbrel) in improving hematopoiesis (i.e. peripheral counts) in patients with FA.
Secondary Objectives:
- Correlation of biological studies to measure the impact of Etanercept (Enbrel) on Tumor Necrosis Factor - α (TNF-α) production.
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) 1. Cells from FA patients exhibit hypersensitivity to alkylating agents such as mitomycin C and diepoxybutane (DEB). Currently, FA is diagnosed by testing for chromosome breakage after lymphocyte stimulation and exposure to mitomycin C (MMC) or diepoxybutane (DEB) 2. Chromosome fragility, defined by an increased percentage of chromosome breaks, is diagnostic for FA3. Although it is the most common form of constitutional aplastic anemia it is very uncommon and the true incidence of FA is not known. A total of 754 patients from North America with the DEB confirmed diagnoses of FA were registered into the International Fanconi Anemia registry (IFAR) by 2001. The major cause of morbidity and mortality for children with FA is bone marrow failure that occurs in the majority of children in the first and second decades of life. Attempts to culture bone marrow progenitors in vitro from FA patients demonstrate decreased numbers of myeloid and erythroid colonies, which is consistent with clinical bone marrow failure.
Current treatment for FA relies upon hematological support in the form of transfusions once advanced marrow failure occurs. Patients with FA do not respond to anti-thymocyte globulin or cyclosporine (typical treatments for acquired aplastic anemia), but 50% improve with androgen preparations, with a median prolongation of life of 2 years in responders (from 16 years to 18 years of age at death) although relapses are inevitable. Androgen therapy causes significant liver toxicity, virilization and risk of hepatic adenoma or carcinoma. Patients who do not respond to these modalities are treated with stem cell transplantation, with its associated toxicities from the transplant conditioning regimens, graft-versus-host disease and increased risk of post transplant malignancy compared to patients without FA. Five-year survival after a matched sibling transplant is approximately 65%. After an unrelated donor transplant, five-year survival is about 30%. The natural history of this disease is one of eventual death by age 10 to 20 years from progressive marrow failure or from conversion to AML (in approximately 10% of patients). Thus there is clearly a need for an effective and early therapy with better toxicity profile.
Studies in both animals and human subjects indicate that high levels of systemic TNF-α and increased sensitivity of hematopoietic progenitors to TNF-α plays a key role in pathogenesis of bone marrow failure in patients with FA. This suggests a possible benefit in supporting hematopoiesis with anti-TNF-α receptor Fc fusion protein (Etanercept; Enbrel) in children with FA. This study proposes to treat patients with FA and early marrow failure with Etanercept (Enbrel), a medication used to treat rheumatoid arthritis. The results of the proposed project will use important preclinical data (see below) to support the development of a novel therapeutic approach for treatment of marrow failure in FA. Etanercept (Enbrel) will prevent the progressive marrow failure and associated complications without the need for transplant and if found to be effective, this treatment can be included in standard clinical care of FA patients, potentially for many years.
- Conditions
- Fanconi Anemia
- Being tested
- Etanercept
- Keywords
- Fanconi Anemia, Hemic and Lymphatic Diseases, Anti-Rheumatic Agents, Anemia, Hypoplastic, Congenital, DNA Repair-Deficiency Disorders, Congenital, Hereditary, and, Neonatal Diseases and Abnormalities
- Medical subject headings
- Fanconi Anemia, Hemic and Lymphatic Diseases, Anemia, Hypoplastic, Congenital, DNA Repair-Deficiency Disorders, Congenital, Hereditary, and Neonatal Diseases and Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Also called Enbrel
All qualified subjects receive 24 weekly subcutaneous injections of Etanercept.
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | Not described Receives: Drug: Etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure.
Measured: 24 months
To assess efficacy of Etanercept (Enbrel) in improving hematopoiesis (i.e. peripheral counts) in patients with FA.
Measured: 24 months
Secondary outcomes (1)
Correlation of biological studies to measure the impact of Etanercept (Enbrel) on Tumor Necrosis Factor - alpha (TNF-alpha) production.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2009 (estimated)
- Study startOct 2005
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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
- Early Phase 1
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Stella M. Davies, MBBSPhd MRCP, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00965666
- Sponsor's protocol ID
- 05-07-24
- Status last verified
- Mar 2012
- First submitted
- 24 Aug 2009
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Etanercept (Enbrel) in Children With Fanconi Anemia and Early Bone Marrow Failure: A Pilot Study
- ClinicalTrials.gov ID
- NCT00965666
- Acronym / sponsor ID
- 05-07-24
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi Anemia, Hemic and Lymphatic Diseases, Anti-Rheumatic Agents, Anemia, Hypoplastic, Congenital, DNA Repair-Deficiency Disorders, Congenital, Hereditary, and, Neonatal Diseases and Abnormalities
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Oct 2005
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 25 Aug 2009 (estimated)
- Results
- Not posted in the source record
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 evaluate the safety of the drug Etanercept (Enbrel) and to determine if this drug can help in the treatment of early bone marrow failure in patients with Fanconi anemia.
Detailed description
Patients with FA are treated with blood products (transfusions), injections to stimulate white blood cell production, and/or androgen therapy once they reach advanced stages of bone marrow failure. Although these therapies lead to temporary improvement in the blood counts, they are associated with potential serious side effects. Currently, the only known potential cure for bone marrow failure in Fanconi Anemia is a stem cell transplant, which is usually done at the late stages of bone marrow failure and is again associated with significant toxicity.
Studies show that patients with FA are very sensitive to and produce unusually high levels of a protein called tumor necrosis factor alpha (TNF-α) that causes bone marrow cells to die. We will study whether a drug called Etanercept that reduces levels of TNF-α will delay or prevent the progressive bone marrow failure associated with FA. Etanercept has been successfully used in children with arthritis.
Primary Objectives:
- To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure.
- To assess efficacy of Etanercept (Enbrel) in improving hematopoiesis (i.e. peripheral counts) in patients with FA.
Secondary Objectives:
- Correlation of biological studies to measure the impact of Etanercept (Enbrel) on Tumor Necrosis Factor - α (TNF-α) production.
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) 1. Cells from FA patients exhibit hypersensitivity to alkylating agents such as mitomycin C and diepoxybutane (DEB). Currently, FA is diagnosed by testing for chromosome breakage after lymphocyte stimulation and exposure to mitomycin C (MMC) or diepoxybutane (DEB) 2. Chromosome fragility, defined by an increased percentage of chromosome breaks, is diagnostic for FA3. Although it is the most common form of constitutional aplastic anemia it is very uncommon and the true incidence of FA is not known. A total of 754 patients from North America with the DEB confirmed diagnoses of FA were registered into the International Fanconi Anemia registry (IFAR) by 2001. The major cause of morbidity and mortality for children with FA is bone marrow failure that occurs in the majority of children in the first and second decades of life. Attempts to culture bone marrow progenitors in vitro from FA patients demonstrate decreased numbers of myeloid and erythroid colonies, which is consistent with clinical bone marrow failure.
Current treatment for FA relies upon hematological support in the form of transfusions once advanced marrow failure occurs. Patients with FA do not respond to anti-thymocyte globulin or cyclosporine (typical treatments for acquired aplastic anemia), but 50% improve with androgen preparations, with a median prolongation of life of 2 years in responders (from 16 years to 18 years of age at death) although relapses are inevitable. Androgen therapy causes significant liver toxicity, virilization and risk of hepatic adenoma or carcinoma. Patients who do not respond to these modalities are treated with stem cell transplantation, with its associated toxicities from the transplant conditioning regimens, graft-versus-host disease and increased risk of post transplant malignancy compared to patients without FA. Five-year survival after a matched sibling transplant is approximately 65%. After an unrelated donor transplant, five-year survival is about 30%. The natural history of this disease is one of eventual death by age 10 to 20 years from progressive marrow failure or from conversion to AML (in approximately 10% of patients). Thus there is clearly a need for an effective and early therapy with better toxicity profile.
Studies in both animals and human subjects indicate that high levels of systemic TNF-α and increased sensitivity of hematopoietic progenitors to TNF-α plays a key role in pathogenesis of bone marrow failure in patients with FA. This suggests a possible benefit in supporting hematopoiesis with anti-TNF-α receptor Fc fusion protein (Etanercept; Enbrel) in children with FA. This study proposes to treat patients with FA and early marrow failure with Etanercept (Enbrel), a medication used to treat rheumatoid arthritis. The results of the proposed project will use important preclinical data (see below) to support the development of a novel therapeutic approach for treatment of marrow failure in FA. Etanercept (Enbrel) will prevent the progressive marrow failure and associated complications without the need for transplant and if found to be effective, this treatment can be included in standard clinical care of FA patients, potentially for many years.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: Etanercept |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have a diagnosis of FA proven by a DEB test conducted in the cytogenetics lab of Dr. Arleen Auerbach, Rockefeller University Hospital.
- Patients must have evidence of early marrow failure i.e. reduction in at least one cell line on two separate occasions at least one month apart e.g. platelet count of < 100,000 per cubic millimeter, hemoglobin < 9 gm/dl and/or absolute neutrophil count (ANC) of < 1000
- Negative pregnancy test (conducted via serum β-HCG screen) - done before the first dose of study drug in all women (except those surgically sterile, at least 5 years postmenopausal, or under the age of 10 years)
- Sexually active patients of childbearing potential must agree to use medically acceptable form of contraception during screening and throughout the study
- Patients or designees must have the ability to self-inject investigational product or have a care giver at home who can administer subcutaneous injections
Key exclusion criteria (22 listed)
- Patients < 4 yrs of age
- Patients with advanced marrow failure i.e. transfusion dependent, will not be eligible as we anticipate that stem cell depletion will already be advanced at this stage.
- Patients currently enrolled in another investigational device or drug trial(s) (defined as a drug not approved by the FDA), or who have received other investigational agent(s) within 28 days of baseline visit with the exception of CCHMC IRB protocol # 03-9-11, "Thyroid Hormone in Children with Fanconi Anemia"
- Patients on androgen therapy
- Patients who have received immunosuppressive agents within the last 3 months prior to enrollment
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 |
|---|---|---|
| EtanerceptAlso: EnbrelAll qualified subjects receive 24 weekly subcutaneous injections of Etanercept. | Drug | Open Label |
Primary outcome
To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure.
Time frame: 24 months
To assess efficacy of Etanercept (Enbrel) in improving hematopoiesis (i.e. peripheral counts) in patients with FA.
Time frame: 24 months
1 secondary outcome
Correlation of biological studies to measure the impact of Etanercept (Enbrel) on Tumor Necrosis Factor - alpha (TNF-alpha) production.
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
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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.
Stella M. Davies, MBBSPhd MRCP principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Etanercept in people with Fanconi Anemia, run by Children's Hospital Medical Center, Cincinnati 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 7 inclusion and 22 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 14 Sep 2020. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure. (time frame: 24 months). The study lists 2 primary outcomes in all. 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 14 Sep 2020.