Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia (LeucineDBA)
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.
|Diamond Blackfan Anemia Blackfan Diamond Syndrome DBA Congenital Hypoplastic Anemia Pure Red Cell Aplasia||Drug: leucine||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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|
- Response to Leucine in Transfusion dependent patients with Diamond Blackfan Anemia [ Time Frame: Patients will take leucine for 9 months. The study is expected to take 12-15 months to complete. ]
The primary outcome is the type of response observed at 9 months (and 6 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 1% and any increase in transfusion interval from baseline. (Baseline reticulocytes range from 0.1 to 0.5 and transfusions are usually performed every 3 weeks. An increase of reticulocyte counts to over 1 to 1.5% and any increase in transfusion interval will be considered a PR.)
- No response (NR): no change in transfusion requirements and no significant change in Hb or reticulocytes (or any response that does not satisfy the conditions of either a PR or CR)
- Progression: worsening of disease as defined by the need for more frequent transfusions
- Side effects of leucine in transfusion-dependent DBA patients [ Time Frame: Total study 12-15 months ]Secondary outcomes include safety parameters such as type, frequency, and severity of adverse events and relationship to leucine.
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
No alternative treatment arm
Dosage of leucine will be dependent on body surface area (BSA):
leucine 700 mg/m2/dose by mouth three times a day
Other Name: leucine, L-leucine
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01362595
|United States, Arizona|
|Phoenix Children's Hospital|
|Phoenix, Arizona, United States, 85016|
|United States, California|
|Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|United States, Indiana|
|Riley Hospital for Children|
|Indianapolis, Indiana, United States, 46202|
|United States, Kentucky|
|University of Louisville|
|Louisville, Kentucky, United States, 40202|
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|University of Michigan C.S. Mott Children's Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, Missouri|
|University of Missouri-Columbia Women's and Children's Hospital|
|Columbia, Missouri, United States, 65201|
|United States, Nevada|
|Children's Specialty Center of Nevada|
|Las Vegas, Nevada, United States, 89109|
|United States, New York|
|Cohen Children's Medical Center of New York|
|New Hyde Park, New York, United States, 11040|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|UT Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Adrianna Vlachos, MD||North Shore- Long Island Jewish Medical Center; Cohen Children's Medical Center of NY|