Blackfan Diamond Syndrome, Congenital Hypoplastic Anemia, DBA, Diamond Blackfan Anemia, Pure Red Cell Aplasia
Conditions
Keywords
leucine administration, red blood cell transfusion, Diamond Blackfan anemia
Brief summary
This study will determine the safety and possibility of giving the amino acid, leucine, in patients with Diamond Blackfan anemia(DBA)who are on dependent on red blood cell transfusions. The leucine is expected to produce a response in patients with DBA to the point where red blood cell production is increased. Red cell transfusions can then be less frequent or possibly discontinued. The investigators will study the side effects, if any, of giving leucine to DBA patients. Leucine levels of leucine will be obtained at baseline and during the study. The drug leucine will be provided in capsule form and taken 3 times a day for a total of 9 months.
Detailed description
Leucine will be provided to participants in the form of a capsule and will be taken three times daily. Blood hemoglobin levels will be monitored every 3-4 weeks for 9 months. The entire study will last 12-15 months in length. Subjects must be two years of age or older and on transfusion for more than six months prior to enrollment.
Interventions
DRUGleucine
Dosage of leucine will be dependent on body surface area (BSA): leucine 700 mg/m2/dose by mouth three times a day
Sponsors
Northwell Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosed with Diamond Blackfan anemia as published in British Journal of Hematology * transfusion dependent * age 2 years and older * adequate renal function * adequate liver function * negative B-HCG if patient is a menstruating female and documentation of adequate contraception * signed informed consent
Exclusion criteria
* Known hypersensitivity to branched chain amino acids * Diagnosis of an inborn error of amino acid metabolism disorder * Prior hematopoietic stem cell transplantation * Pregnancy, or plans to become pregnant during duration of trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia | 9 Months | The primary outcome is the type of response observed at 9 months. Response to treatment can be one of the following: 1. Complete response (CR): Hb \> 9 gm/dL and transfusion-independence as defined in DBA 2. Partial response (PR): Hb \< 9 gm/dL and increased reticulocyte count to greater than baseline. 3. No response (NR): no change in transfusion requirements and no significant change reticulocyte count from baseline 4. Progression: worsening of disease as defined by the need for more frequent transfusions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe Adverse Events Attributable to Leucine | 9 months | Adverse events occurring while participants were on Leucine |
Countries
United States
Participant flow
Recruitment details
55 subjects were screened and of those 12 did not meet eligibility criteria
Participants by arm
| Arm | Count |
|---|---|
| Leucine No alternative treatment arm
leucine: Dosage of leucine will be dependent on body surface area (BSA): leucine 700 mg/m2/dose by mouth three times a day | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen failure | 10 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Leucine |
|---|---|
| Age, Categorical <=18 years | 34 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 10.4 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 43 |
| other Total, other adverse events | 0 / 43 |
| serious Total, serious adverse events | 0 / 43 |
Outcome results
Primary
Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia
The primary outcome is the type of response observed at 9 months. Response to treatment can be one of the following: 1. Complete response (CR): Hb \> 9 gm/dL and transfusion-independence as defined in DBA 2. Partial response (PR): Hb \< 9 gm/dL and increased reticulocyte count to greater than baseline. 3. No response (NR): no change in transfusion requirements and no significant change reticulocyte count from baseline 4. Progression: worsening of disease as defined by the need for more frequent transfusions
Time frame: 9 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Leucine | Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia | Complete Hematologic Response | 2 Participants |
| Leucine | Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia | Partial hematologic response | 5 Participants |
| Leucine | Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia | No hematologic response | 36 Participants |
| Leucine | Response to Leucine in Transfusion Dependent Patients With Diamond Blackfan Anemia | Progression | 0 Participants |
Secondary
Severe Adverse Events Attributable to Leucine
Adverse events occurring while participants were on Leucine
Time frame: 9 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Leucine | Severe Adverse Events Attributable to Leucine | No Adverse events | 41 Participants |
| Leucine | Severe Adverse Events Attributable to Leucine | Withdrew early | 2 Participants |