Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Use of Novel Therapies to Reconstitute Blood Cell Production and Promote Organ Performance Using Bone Marrow Failure as a Model: a Pilot, Phase I/II Study of the Amino Acid Leucine in the Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia

Conditions
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DBA, Diamond Blackfan Anemia, Blackfan Diamond Syndrome, Congenital Hypoplastic Anemia, Pure Red Cell Aplasia

Intervention / Treatment
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* Drug: leucine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Leucine<br>No alternative treatment arm | Drug: leucine<br>* Dosage of leucine will be dependent on body surface area (BSA): leucine 700 mg/m2/dose by mouth three times a day<br>* Other names: L-leucine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: Complete response (CR): Hb > 9 gm/dL and transfusion-independence as defined in DBA Partial response (PR): Hb < 9 gm/dL and increased reticulocyte count to greater than baseline. No response (NR): no change in transfusion requirements and no significant change reticulocyte count from baseline Progression: worsening of disease as defined by the need for more frequent transfusions | 9 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Adverse Events Attributable to Leucine | Adverse events occurring while participants were on Leucine | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leucine administration, red blood cell transfusion, Diamond Blackfan anemia