Ignite Creation Date:
2024-05-06 @ 10:15 AM
Last Modification Date:
2024-10-26 @ 12:27 PM
Study NCT ID:
NCT03206086
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2017-06-30
Brief Title:
Eltrombopag for People With Fanconi Anemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Eltrombopag for Patients With Fanconi Anemia
Status:
RECRUITING
Status Verified Date:
2024-07-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Fanconi anemia is a genetic disease Some people with it have reduced blood cell counts This means their bone marrow no longer works properly These people may need blood transfusions for anemia low red blood cells or low platelet counts or bleeding Researchers want to see if a new drug will help people with this disease
Objective
To find out if a new drug eltrombopag is effective in people with Fanconi anemia To know how long the drug needs to be given to improve blood counts
Eligibility
People at least 6 years old with Fanconi anemia with reduced blood cell counts
Design
Participants will be screened with blood and urine tests They will repeat this before starting to take the study drug
Participants will take eltrombopag pills by mouth once a day for 24 weeks They will be monitored closely for side effects
Participants will have blood tests every 2 weeks while on eltrombopag
Participants will visit NIH 3 months and 6 months after starting eltrombopag At these visits participants will
Answer questions about their medical history how they are feeling and their quality of life
Have a physical exam
Have blood and urine tests
Have a bone marrow sample taken by needle from the hip The area will be numbed
If participants blood cell counts improve they might join the extended access part of the study They will continue taking eltrombopag for 3 years and sign a different consent
After 24 weeks of treatment if there is no improvement in blood cell counts participants will stop taking eltrombopag They will return for an optional follow-up visit that repeats the study visits
Fanconi anemia is a genetic disease Some people with it have reduced blood cell counts This means their bone marrow no longer works properly These people may need blood transfusions for anemia low red blood cells or low platelet counts or bleeding Researchers want to see if a new drug will help people with this disease
Objective
To find out if a new drug eltrombopag is effective in people with Fanconi anemia To know how long the drug needs to be given to improve blood counts
Eligibility
People at least 6 years old with Fanconi anemia with reduced blood cell counts
Design
Participants will be screened with blood and urine tests They will repeat this before starting to take the study drug
Participants will take eltrombopag pills by mouth once a day for 24 weeks They will be monitored closely for side effects
Participants will have blood tests every 2 weeks while on eltrombopag
Participants will visit NIH 3 months and 6 months after starting eltrombopag At these visits participants will
Answer questions about their medical history how they are feeling and their quality of life
Have a physical exam
Have blood and urine tests
Have a bone marrow sample taken by needle from the hip The area will be numbed
If participants blood cell counts improve they might join the extended access part of the study They will continue taking eltrombopag for 3 years and sign a different consent
After 24 weeks of treatment if there is no improvement in blood cell counts participants will stop taking eltrombopag They will return for an optional follow-up visit that repeats the study visits
Detailed Description:
Fanconi anemia FA is a rare genetic disease that often presents as a bone marrow failure BMF syndrome but also can affect any other organ Etiologically loss of function mutations in more than 21 different gene members of the FA core complex ie FANCA-FANCV have been associated with FA The FA core complex is involved in interstrand cross-link DNA damage repair during cell division Impaired DNA repair causes genomic instability which consequently can cause apoptosis of the cell or malignant transformation In addition to impaired DNA repair mechanisms FA cells exhibit increased sensitivity to pro-inflammatory cytokines eg IFN-gamma TNF-alpha and elevated levels of these cytokines have been associated with bone marrow failure in subjects with FA and other inherited bone marrow failure syndromes
Patients with FA may present with congenital anomalies such as microcephaly or short stature However the failure of the hematopoietic stem cell HSC compartment to produce sufficient numbers of peripheral blood cells and progression to myelodysplastic syndrome MDS and acute myelogenous leukemia AML are the greatest risk factors for morbidity and mortality particular in young patients with FA In a few reported cases spontaneous somatic reversion of inherited mutations has resulted in a selective growth advantage of corrected HSCs that subsequently restored hematopoiesis However therapeutic options are limited in FA Although HSC transplantation outcomes have significantly improved over the past two decades donor availability graft failure and FA-specific transplant toxicities are still significant hurdles towards a curative treatment of FA-associated BMF Moreover attempts at genetic correction of FA are not yet ready for patient care
The thrombopoietin TPO mimetic eltrombopag EPAG has recently been shown to be effective in restoring tri-lineage hematopoiesis in patients with treatment refractory acquired severe aplastic anemia SAA Of particular interest for patients with FA is the observation that EPAG also improves the repair of double strand DNA breaks a mechanism that is impaired in patients with FA Additionally our pre-clinical studies indicate that EPAG evades INF-gamma blockade of signal transduction from the TPO receptor cMPL resulting in improved survival and proliferation of HSCs Based on these clinical and pre-clinical studies we hypothesize that EPAG will improve peripheral blood cell counts in patients with FA and thus reduce morbidity and mortality
This phase II clinical trial proposes to treat patients with FA for 6 months with EPAG to assess safety and efficacy at improving hematological manifestations of FA Responders at 6 months will be able to continue EPAG on the extension part of this protocol for an additional 3 years During this time frame we anticipate further improvement of peripheral blood cells counts that will eventually result in the discontinuation of EPAG after a tapering period Translational studies will explore EPAG effects on DNA repair activity apoptosis global transcriptome and TPO signaling pathways in patient s hematopoietic stem and progenitor cells HSPCs
Patients with FA may present with congenital anomalies such as microcephaly or short stature However the failure of the hematopoietic stem cell HSC compartment to produce sufficient numbers of peripheral blood cells and progression to myelodysplastic syndrome MDS and acute myelogenous leukemia AML are the greatest risk factors for morbidity and mortality particular in young patients with FA In a few reported cases spontaneous somatic reversion of inherited mutations has resulted in a selective growth advantage of corrected HSCs that subsequently restored hematopoiesis However therapeutic options are limited in FA Although HSC transplantation outcomes have significantly improved over the past two decades donor availability graft failure and FA-specific transplant toxicities are still significant hurdles towards a curative treatment of FA-associated BMF Moreover attempts at genetic correction of FA are not yet ready for patient care
The thrombopoietin TPO mimetic eltrombopag EPAG has recently been shown to be effective in restoring tri-lineage hematopoiesis in patients with treatment refractory acquired severe aplastic anemia SAA Of particular interest for patients with FA is the observation that EPAG also improves the repair of double strand DNA breaks a mechanism that is impaired in patients with FA Additionally our pre-clinical studies indicate that EPAG evades INF-gamma blockade of signal transduction from the TPO receptor cMPL resulting in improved survival and proliferation of HSCs Based on these clinical and pre-clinical studies we hypothesize that EPAG will improve peripheral blood cell counts in patients with FA and thus reduce morbidity and mortality
This phase II clinical trial proposes to treat patients with FA for 6 months with EPAG to assess safety and efficacy at improving hematological manifestations of FA Responders at 6 months will be able to continue EPAG on the extension part of this protocol for an additional 3 years During this time frame we anticipate further improvement of peripheral blood cells counts that will eventually result in the discontinuation of EPAG after a tapering period Translational studies will explore EPAG effects on DNA repair activity apoptosis global transcriptome and TPO signaling pathways in patient s hematopoietic stem and progenitor cells HSPCs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 17-H-0121 | None | None | None |