Pilot Study of Metformin for Patients With Fanconi Anemia
Primary Purpose
Fanconi Anemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
metformin HCl
Sponsored by
About this trial
This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi Anemia, Metformin
Eligibility Criteria
Inclusion Criteria:
- 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
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
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- Boston Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment arm
Arm Description
Receive metformin HCl
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03398824
First Posted
December 13, 2017
Last Updated
November 4, 2022
Sponsor
Boston Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03398824
Brief Title
Pilot Study of Metformin for Patients With Fanconi Anemia
Official Title
Pilot Study of Metformin for Patients With Fanconi Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
March 29, 2018 (Actual)
Primary Completion Date
October 9, 2020 (Actual)
Study Completion Date
October 9, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston Children's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia
Keywords
Fanconi Anemia, Metformin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Receive metformin HCl
Intervention Type
Drug
Intervention Name(s)
metformin HCl
Intervention Description
Receive metformin HCl
Primary Outcome Measure Information:
Title
Hematologic Response
Description
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
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Akiko Shimamura, MD, PhD
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35500223
Citation
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.
Results Reference
derived
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Pilot Study of Metformin for Patients With Fanconi Anemia
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