|May 20, 2011
|November 19, 2015
|September 2016 (final data collection date for primary outcome measure)
|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. ] [ Designated as safety issue: Yes ]
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
|To determine the feasibility of administering the amino acid leucine and to determine the pharmacokinetics of leucine administration in patients with Diamond Blackfan anemia [ Time Frame: Leucine levels will be monitored with PK testing at baseline, week 2, 1 month, 3 months, 5 months and 9 months of administration +/- one week. ] [ Designated as safety issue: Yes ]
Normal reference blood levels of leucine by age as per Pass,et.al.are described as follows:
Infants 9 to 24 months: 0.59-2.03 mg/dL (45-155 micromol/L) Children 3 to 10 years: 0.73-2.33 mg/dL (56-178 micromol/L) Children 6 to 18 years: 1.03-2.28 mg/dL (79-174 micromol/L) Adults: 0.98-2.29 mg/dL (75-175 micromol/L) This study will evaluate the level of leucine which can be attributed to side effects in relation to decreased or elevated normal values of Leucine.
|Complete list of historical versions of study NCT01362595 on ClinicalTrials.gov Archive Site
|Side effects of leucine in transfusion-dependent DBA patients [ Time Frame: Total study 12-15 months ] [ Designated as safety issue: Yes ]
Secondary outcomes include safety parameters such as type, frequency, and severity of adverse events and relationship to leucine.
|To determine the efficacy of leucine to produce a hematologic response in patients with DBA. [ Time Frame: After 9 months of drug administration will assess hemoglobin response to leucine ] [ Designated as safety issue: Yes ]
At 9 months of treatment a response will betermined by looking at the hemoglobin:
Complete response- Hgb >9 gm/dl and weaned off transfusion
Partial response- Hgb <9 gm/dl with an increase in reticulocyte count and transfusion interval is increased
No response- No change in transfusion requirement, no change in hgb or reticulocyte count
|A Pilot, Phase I/II Study of the Amino Acid Leucine in the Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
|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
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.
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.
|Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- Diamond Blackfan Anemia
- Blackfan Diamond Syndrome
- Congenital Hypoplastic Anemia
- Pure Red Cell Aplasia
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
No alternative treatment arm
Intervention: Drug: leucine
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|September 2016 (final data collection date for primary outcome measure)
- 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
- 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
|2 Years and older
|Adrianna Vlachos, North Shore Long Island Jewish Health System
||Adrianna Vlachos, MD
||North Shore- Long Island Jewish Medical Center; Cohen Children's Medical Center of NY