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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02386267
Other study ID # Ru0001
Secondary ID
Status Recruiting
Phase Phase 2
First received February 18, 2015
Last updated March 5, 2015
Start date September 2014
Est. completion date March 2016

Study information

Verified date March 2015
Source Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache
Contact Natalia - SMETANINA, MD, PhD
Phone +7 985 647 13 05
Email Nataliya.Smetanina@fccho-moscow.ru
Is FDA regulated No
Health authority Russia: Ministry of Health of the Russian Federation
Study type Interventional

Clinical Trial 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 adipose tissue.

Several preclinical studies with DBA lymphocytes exposed to various L-leucine doses, have demonstrated that protein synthesis can be increased by using high doses L-leucine.

Recent clinical data on L-leucine therapeutic use have demonstrated increase the hemoglobin level and transfusion independence in patients with DBA and 5q-syndrom.

These data support the rationale for clinical trial on L-leucine use as a therapeutic agent for DBA patients.


Description:

Experimental: one arm L-leucine , dose- 700mg/m2 , per os, 3 time a day, 6 months


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date March 2016
Est. primary completion date March 2015
Accepts healthy volunteers No
Gender Both
Age group 1 Year to 20 Years
Eligibility Inclusion Criteria:

- signed Informed Consent Form

- diagnosed Diamond Blackfan Anemia

- transfusion dependen?e

- adequate renal function

- adequate liver function

- negative B-HCG and adequate contraception

Exclusion Criteria:

- known hypersensitivity to branched chain amino acids

- diagnosed AA metabolism disorder

- prior HSCT

- pregnancy or planning to become pregnant

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
L-leucine
L-leucine pills per os for 6 months

Locations

Country Name City State
Russian Federation Federal Scientific Clinical Centre of Pediatric Hematology Oncology Immunology n.a. Dmitry Rogachev Moscow

Sponsors (1)

Lead Sponsor Collaborator
Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type Measure Description Time frame Safety issue
Primary Hemoglobin level Response to the 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, increased reticulocyte count > 1% and any increase in transfusion interval from baseline.
No response (NR): no change in transfusion requirements and no significant change in Hb or reticulocytes
Progression: worsening of disease as defined by the need for more frequent transfusions
every 4 weeks for 12 months No
Secondary Side effects of L-leucine in transfusion-dependent DBA patients for one year every 4 weeks for 12 moths Yes
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Terminated NCT00001962 - A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure Phase 2
Completed NCT01362595 - Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia Phase 1/Phase 2
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Terminated NCT01464164 - Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia Phase 1/Phase 2
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