Clinical Trial: L-leucine in Diamond Blackfan Anemia Patients

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Therapeutic Use of the Amino Acid Leucine in the Treatment of Transfusion-Dependent Diamond Blackfan Anemia Patients

Brief Summary:

Diamond-Blackfan anemia (DBA) is a rare congenital syndrome associated with physical anomalies, short stature, red cell aplasia, and an increased risk of malignancy.

Mutations affecting genes encoding ribosomal proteins cause DBA. Genetic studies have identified heterozygous mutations in at least one of eight ribosomal protein genes in up to 50% of cases.

25% of patients carry a mutation in the ribosomal protein (RP)S19 gene, whereas mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5 are rare.

p53 activation has been identified as a key component in the pathophysiology of DBA after cellular and molecular studies. Other potential mechanisms that warrant further investigation include impaired translation as the result of ribosomal insufficiency, which may be ameliorated by Leucine supplementation.

Despite significant improvements in understanding of the pathophysiology of Diamond Blackfan anemia (DBA), there have been few advances in therapy. The cornerstones of treatment remain corticosteroids,chronic red blood cell transfusions, and hematopoietic stem cell transplantation, each of which is fraught with complications. Other treatments have been shown to be effective in only a few patients or in individual case reports : IL-3, cyclosporine (alone or in combination with steroids), metaclopramide. Gene therapy is still a part of research programs.

There are some indications that the Amino Acid (AA) L-leucine, a translation enhancer, may have some efficacy in DBA and 5q-syndrome, which has the same altered ribosome functions as the DBA. L-leucine is an essential AA that is unique among the branched-chain AA acting as a nutrient regulator of protein synthesis in skeletal muscle and

Detailed Summary: Experimental: one arm L-leucine , dose- 700mg/m2 , per os, 3 time a day, 6 months
Sponsor: Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmit

Current Primary Outcome: Hemoglobin level [ Time Frame: every 4 weeks for 12 months ]

Response to the 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, increased reticulocyte count > 1% and any increase in transfusion interval from baseline.
  3. No response (NR): no change in transfusion requirements and no significant change in Hb or reticulocytes
  4. Progression: worsening of disease as defined by the need for more frequent transfusions


Original Primary Outcome: Same as current

Current Secondary Outcome: Side effects of L-leucine in transfusion-dependent DBA patients for one year [ Time Frame: every 4 weeks for 12 moths ]

Original Secondary Outcome: Same as current

Information By: Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmit

Dates:
Date Received: February 18, 2015
Date Started: September 2014
Date Completion: March 2016
Last Updated: March 5, 2015
Last Verified: March 2015