Ignite Creation Date:
2024-05-06 @ 6:54 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05828108
Status:
RECRUITING
Last Update Posted:
2024-04-10
First Post:
2023-04-22
Brief Title:
Study of the Selective GlyT1 Inhibitor Bitopertin for Steroid-Refractory Diamond-Blackfan Anemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Intra-Patient Dose-Escalation Study of the Selective GlyT1 Inhibitor Bitopertin for Steroid-Refractory Diamond-Blackfan Anemia
Status:
RECRUITING
Status Verified Date:
2024-04-08
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
Diamond-Blackfan anemia DBA is an inherited disease that affects the bone marrow People with DBA have chronic anemia that can be severe Many must have frequent transfusions of red blood cells Current treatments for DBA all have risks of serious side effects Better treatments are needed
Objective
To test a new drug bitopertin in people with DBA
Eligibility
People aged 18 or older with DBA
Design
Participants will be screened They will have a physical exam they will have blood tests and a test of their heart function They will have a bone marrow biopsy An area of their hip will be numbed and a needle will be inserted to remove a sample of tissue from inside the bone
Bitopertin is a pill taken by mouth Participants will take the drug once a day every day for 8 months They will start with a low dose of the drug the dosage may increase gradually over time They will keep a diary to record each dose
Participants will have blood tests every 4 weeks This may be done in the clinic Participants may also have telehealth visits they can have blood drawn at a local lab and sent to the researchers
The bone marrow biopsy and other tests will be repeated after 8 months
Participants who have a positive response to bitopertin will be invited to enter an extended phase of the trial They may continue to take the drug for 3 more years
Those who choose not to continue in the extended phase may have a follow-up visit 6 months after they stop taking the drug
Diamond-Blackfan anemia DBA is an inherited disease that affects the bone marrow People with DBA have chronic anemia that can be severe Many must have frequent transfusions of red blood cells Current treatments for DBA all have risks of serious side effects Better treatments are needed
Objective
To test a new drug bitopertin in people with DBA
Eligibility
People aged 18 or older with DBA
Design
Participants will be screened They will have a physical exam they will have blood tests and a test of their heart function They will have a bone marrow biopsy An area of their hip will be numbed and a needle will be inserted to remove a sample of tissue from inside the bone
Bitopertin is a pill taken by mouth Participants will take the drug once a day every day for 8 months They will start with a low dose of the drug the dosage may increase gradually over time They will keep a diary to record each dose
Participants will have blood tests every 4 weeks This may be done in the clinic Participants may also have telehealth visits they can have blood drawn at a local lab and sent to the researchers
The bone marrow biopsy and other tests will be repeated after 8 months
Participants who have a positive response to bitopertin will be invited to enter an extended phase of the trial They may continue to take the drug for 3 more years
Those who choose not to continue in the extended phase may have a follow-up visit 6 months after they stop taking the drug
Detailed Description:
Study Description
Diamond-Blackfan anemia DBA is an inherited bone marrow failure syndrome characterized by selective erythroid defects In DBA a defect in erythroid ribosome biosynthesis creates an asynchrony between protein synthesis of globin chains and heme wherein the continued production of free heme without sufficient globin is toxic to cells Bitopertin prevents the uptake of glycine through the GlyT1 transporter reducing the synthesis of 5- aminolevulinic acid the rate-limiting step in heme synthesis which in turn leads to a significant reduction in intracellular heme
We hypothesize that bitopertin will rescue DBA by rebalancing heme and globin chain production and reducing the toxicity to the hematopoietic cells that the excess heme causes Thus we propose a phase III pilot single-arm intra-patient dose-escalation trial of bitopertin for the treatment of steroid-refractory DBA
Objectives
Primary Objective Efficacy of bitopertin in treating Diamond- Blackfan anemia
Secondary Objectives
Examine the safety and tolerability of bitopertin in treating Diamond-Blackfan anemia
Examine the maintenance of response and relapse rates of Diamond-Blackfan anemia during long-term bitopertin use
Examine the effects of long-term treatment of Diamond-Blackfan anemia with bitopertin on clonal evolution survival and health- related quality of life metrics
TertiaryExploratory Objectives
Evaluate the impact of bitopertin on stem cell and erythroid cell dynamics in the Diamond-Blackfan anemia through correlative and translational studies
Examine the pharmacology of bitopertin in Diamond-Blackfan anemia
Endpoints
Primary endpoint
-response rate from drug initiation until 8 months 32 weeks as measured by an increase in pre-transfusion hemoglobin andor either decrease in transfusion rate or transfusion-independence
Secondary endpoints
toxicity profile at 8 months CTCAE criteria
intra-patient maximum tolerated dose at 8 months 32 weeks from drug initiation
response rate after 3 months 12 weeks at the maximum tolerated dose
response rate 3 years post-primary endpoint extension
rate of relapse ongoing for up to 3 years beginning 8 months 32 weeks from drug initiation as demonstrated by new or increasing transfusion requirements andor according to clinical outcome
rate of clonal evolution on bitopertin annually for up to 3 years beginning 8 months 32 weeks from drug initiation as measured by karyotypic histologic and flow cytometric changes
rate of overall survival ongoing for up to 3 years beginning 8 months 32 weeks from drug initiation according to clinical outcomes
Health-related quality of life HRQL annually for up to 3 years beginning 8 months 32 weeks from drug initiation based on questionnaire-based inventory of HRQL
Diamond-Blackfan anemia DBA is an inherited bone marrow failure syndrome characterized by selective erythroid defects In DBA a defect in erythroid ribosome biosynthesis creates an asynchrony between protein synthesis of globin chains and heme wherein the continued production of free heme without sufficient globin is toxic to cells Bitopertin prevents the uptake of glycine through the GlyT1 transporter reducing the synthesis of 5- aminolevulinic acid the rate-limiting step in heme synthesis which in turn leads to a significant reduction in intracellular heme
We hypothesize that bitopertin will rescue DBA by rebalancing heme and globin chain production and reducing the toxicity to the hematopoietic cells that the excess heme causes Thus we propose a phase III pilot single-arm intra-patient dose-escalation trial of bitopertin for the treatment of steroid-refractory DBA
Objectives
Primary Objective Efficacy of bitopertin in treating Diamond- Blackfan anemia
Secondary Objectives
Examine the safety and tolerability of bitopertin in treating Diamond-Blackfan anemia
Examine the maintenance of response and relapse rates of Diamond-Blackfan anemia during long-term bitopertin use
Examine the effects of long-term treatment of Diamond-Blackfan anemia with bitopertin on clonal evolution survival and health- related quality of life metrics
TertiaryExploratory Objectives
Evaluate the impact of bitopertin on stem cell and erythroid cell dynamics in the Diamond-Blackfan anemia through correlative and translational studies
Examine the pharmacology of bitopertin in Diamond-Blackfan anemia
Endpoints
Primary endpoint
-response rate from drug initiation until 8 months 32 weeks as measured by an increase in pre-transfusion hemoglobin andor either decrease in transfusion rate or transfusion-independence
Secondary endpoints
toxicity profile at 8 months CTCAE criteria
intra-patient maximum tolerated dose at 8 months 32 weeks from drug initiation
response rate after 3 months 12 weeks at the maximum tolerated dose
response rate 3 years post-primary endpoint extension
rate of relapse ongoing for up to 3 years beginning 8 months 32 weeks from drug initiation as demonstrated by new or increasing transfusion requirements andor according to clinical outcome
rate of clonal evolution on bitopertin annually for up to 3 years beginning 8 months 32 weeks from drug initiation as measured by karyotypic histologic and flow cytometric changes
rate of overall survival ongoing for up to 3 years beginning 8 months 32 weeks from drug initiation according to clinical outcomes
Health-related quality of life HRQL annually for up to 3 years beginning 8 months 32 weeks from drug initiation based on questionnaire-based inventory of HRQL
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 |
|---|---|---|---|
| 001528-H | None | None | None |