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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01362595
Recruitment Status : Active, not recruiting
First Posted : May 30, 2011
Last Update Posted : September 12, 2019
Information provided by (Responsible Party):
Adrianna Vlachos, Northwell Health

Tracking Information
First Submitted Date  ICMJE May 20, 2011
First Posted Date  ICMJE May 30, 2011
Last Update Posted Date September 12, 2019
Actual Study Start Date  ICMJE June 2013
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
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:
  1. Complete response (CR): Hb > 9 gm/dL and transfusion-independence as defined in DBA
  2. 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.)
  3. 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)
  4. Progression: worsening of disease as defined by the need for more frequent transfusions
Original Primary Outcome Measures  ICMJE
 (submitted: May 26, 2011)
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. ]
Normal reference blood levels of leucine by age as per Pass, 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.
Change History Complete list of historical versions of study NCT01362595 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2011)
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 ]
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
Official Title  ICMJE 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
Brief Summary

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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diamond Blackfan Anemia
  • Blackfan Diamond Syndrome
  • DBA
  • Congenital Hypoplastic Anemia
  • Pure Red Cell Aplasia
Intervention  ICMJE Drug: leucine

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
Study Arms  ICMJE Leucine
No alternative treatment arm
Intervention: Drug: leucine
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 26, 2011)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2019
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01362595
Other Study ID Numbers  ICMJE 12-375B
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adrianna Vlachos, Northwell Health
Study Sponsor  ICMJE Northwell Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Adrianna Vlachos, MD North Shore- Long Island Jewish Medical Center; Cohen Children's Medical Center of NY
PRS Account Northwell Health
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP