Fanconi AnemiaPhase 2NCT03398824
Pilot Study of Metformin for Patients With Fanconi Anemia
A Phase 2 study testing metformin HCl in people with Fanconi Anemia, run by Boston Children's Hospital at 1 site in United States.
Trial summary
This is a single institution, open-label, single arm pilot study of Metformin in patients with Fanconi Anemia (FA) and cytopenias with the primary endpoint of hematologic response. This study will also assess safety, tolerability, and the biologic effects of Metformin in patients with FA. Read more about this study
- Who is it for?
- Ages 6 to 35 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- metformin HCl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2018to 9 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 6 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age > 6 years and ≤35 years
- Lansky/Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for patients <16 years of age (see Appendix A)
- Diagnosis requirement
- Participants must have a clinical diagnosis of Fanconi Anemia.
- Participants must have confirmed diepoxybutane-mitomycin C (DEB/MMC) stress testing to document diagnosis of Fanconi Anemia.
- Patients must have at least one of the following cytopenias: Hemoglobin <10g/dL; Platelets <100k/uL; Absolute neutrophil count <1000/uL
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- Participants must have normal organ function as defined below:
- Hepatic Function : Total bilirubin ≤ 1.5 x upper limit of normal for age; alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 135 U/L
- Renal Function: A serum creatinine based on age/gender as follows:
- Age Maximum Serum Creatinine (mg/dL) Male Female
- to < 2 years 0.6 0.6
- to < 6 years 0.8 0.8
- 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4
- AND
- Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
- Normal cardiac status as documented clinically, otherwise they will need an echocardiogram prior to enrollment
- Serum bicarbonate must be >17.
- Participants of child-bearing or child-fathering potential must agree to use adequate contraception (hormonal birth control; intrauterine device; double barrier method; or total abstinence) throughout their participation, including up until 30 days after last dose of Metformin.
- Patients must be able to swallow pills.
- Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, documented using an institutionally approved informed consent procedure
Who cannot join
- Patients must not have undergone prior bone marrow transplantation.
- Patients must not have very severe aplastic anemia at the time of enrollment which would require bone marrow transplantation (as defined by at least 2 out of the following 3: Absolute Neutrophil Count (ANC) <200k/uL, platelets <20k/uL, absolute reticulocyte count <40k/uL).
- Patients must not be taking any other concurrent medications to improve their hematopoiesis such as androgens or growth factors such as Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), or thrombopoietin (TPO) mimetics. There is a one month wash-out period for prior therapies including androgens.
- Pregnant participants will not be entered on this study given that the effects of Metformin on the developing human fetus are unknown.
- Breastfeeding mothers are not eligible because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Metformin.
- Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Metformin.
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- Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients must not have prior history of symptomatic hypoglycemia over the past year or hypoglycemia with glucose <50mg/dL on screening and baseline laboratory assessments.
- Patients must not have type 1 diabetes mellitus.
- Patients must abstain from alcohol as part of this study.
- Patients must not have a diagnosis of myelodysplastic syndrome or leukemia, or other concurrent malignancy undergoing treatment.
- Patients must not have vitamin B12 deficiency.
- Patients must not have Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency.
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
This is a single institution, open-label, single arm pilot study of Metformin in patients with Fanconi Anemia (FA) and cytopenias with the primary endpoint of hematologic response. This study will also assess safety, tolerability, and the biologic effects of Metformin in patients with FA.
- Conditions
- Fanconi Anemia
- Being tested
- metformin HCl
- Keywords
- Fanconi Anemia, Metformin
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin HClDrug
Receive metformin HCl
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Receive metformin HCl Receives: Drug: metformin HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematologic Response
Hematologic response is defined by specific increases in erythroid, platelet, and neutrophil counts.
Erythroid response: Hemoglobin (Hgb) increase by >1.5g/dL for non-transfusion dependent patients and for patients who are transfusion dependent: Transfusion independence Only transfusions given for Hgb ≤8g/dL or for symptoms will be counted in the response evaluation
Platelet response: If initially <20k/uL to start, then must increase to >20k/UL with an absolute increase of 100%. If initially ≥20k/uL to start, then must have an absolute increase of >30k/UL
Neutrophil response: If initially <500/uL to start, then must increase to >500/uL with an absolute increase of > 250/uL. If initially ≥500/uL to start, then must have an absolute increase of >500/uL
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start29 Mar 2018
- Primary completion9 Oct 2020
- Study completion9 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Akiko Shimamura, Boston Children's Hospital
- Investigators
- Akiko Shimamura, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03398824
- Sponsor's protocol ID
- IRB-P00026540
- Status last verified
- Nov 2022
- First submitted
- 13 Dec 2017
- Last updated
- 29 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Pollard JA, Furutani E, Liu S, Esrick E, Cohen LE, Bledsoe J, Liu CW, Lu K, de Haro MJR, Surralles J, Malsch M, Kuniholm A, Galvin A, Armant M, Kim AS, Ballotti K, Moreau L, Zhou Y, Babushok D, Boulad F, Carroll C, Hartung H, Hont A, Nakano T, Olson T, Sze SG, Thompson AA, Wlodarski MW, Gu X, Libermann TA, D'Andrea A, Grompe M, Weller E, Shimamura A. Metformin for treatment of cytopenias in children and young adults with Fanconi anemia. Blood Adv. 2022 Jun 28;6(12):3803-3811. doi: 10.1182/bloodadvances.2021006490.
PubMed 35500223
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Metformin for Patients With Fanconi Anemia
- ClinicalTrials.gov ID
- NCT03398824
- Acronym / sponsor ID
- IRB-P00026540
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi Anemia, Metformin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 9 Oct 2020 (actual)
- Study completion
- 9 Oct 2020 (actual)
- First posted
- 16 Jan 2018 (actual)
- Results
- Posted 29 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single institution, open-label, single arm pilot study of Metformin in patients with Fanconi Anemia (FA) and cytopenias with the primary endpoint of hematologic response. This study will also assess safety, tolerability, and the biologic effects of Metformin in patients with FA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: metformin HClReceive metformin HCl |
Who may qualify
- Ages
- 6 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Age > 6 years and ≤35 years
- Lansky/Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for patients <16 years of age (see Appendix A)
- Diagnosis requirement
- Participants must have a clinical diagnosis of Fanconi Anemia.
- Participants must have normal organ function as defined below:
Key exclusion criteria (13 listed)
- Patients must not have undergone prior bone marrow transplantation.
- Patients must not have very severe aplastic anemia at the time of enrollment which would require bone marrow transplantation (as defined by at least 2 out of the following 3: Absolute Neutrophil Count (ANC) <200k/uL, platelets <20k/uL, absolute reticulocyte count <40k/uL).
- Patients must not be taking any other concurrent medications to improve their hematopoiesis such as androgens or growth factors such as Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), or thrombopoietin (TPO) mimetics. There is a one month wash-out period for prior therapies including androgens.
- Pregnant participants will not be entered on this study given that the effects of Metformin on the developing human fetus are unknown.
- Breastfeeding mothers are not eligible because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Metformin.
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 |
|---|---|---|
| metformin HClReceive metformin HCl | Drug | Treatment arm |
Primary outcome
Hematologic Response
Time frame: 6 months
Hematologic response is defined by specific increases in erythroid, platelet, and neutrophil counts. Erythroid response: Hemoglobin (Hgb) increase by >1.5g/dL for non-transfusion dependent patients and for patients who are transfusion dependent: Transfusion independence Only transfusions given for Hgb ≤8g/dL or for symptoms will be counted in the response evaluation Platelet response: If initially <20k/uL to start, then must increase to >20k/UL with an absolute increase of 100%. If initially ≥20k/uL to start, then must have an absolute increase of >30k/UL Neutrophil response: If initially <500/uL to start, then must increase to >500/uL with an absolute increase of > 250/uL. If initially ≥500/uL to start, then must have an absolute increase of >500/uL
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35500223Pollard JA, Furutani E, Liu S, Esrick E, Cohen LE, Bledsoe J, Liu CW, Lu K, de Haro MJR, Surralles J, Malsch M, Kuniholm A, Galvin A, Armant M, Kim AS, Ballotti K, Moreau L, Zhou Y, Babushok D, Boulad F, Carroll C, Hartung H, Hont A, Nakano T, Olson T, Sze SG, Thompson AA, Wlodarski MW, Gu X, Libermann TA, D'Andrea A, Grompe M, Weller E, Shimamura A. Metformin for treatment of cytopenias in children and young adults with Fanconi anemia. Blood Adv. 2022 Jun 28;6(12):3803-3811. doi: 10.1182/bloodadvances.2021006490.
- Individual participant dataSharing planned: Undecided
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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.
Akiko Shimamura, MD, PhD principal investigator
Boston Children's Hospital
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 metformin HCl in people with Fanconi Anemia, run by Boston Children's Hospital 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 21 inclusion and 13 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 29 Nov 2022. 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 29 Nov 2022). 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?
Hematologic Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03398824, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022.