Clinical Trial: Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Treatmen

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 Summary:

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.


Sponsor: Northwell Health

Current Primary Outcome: 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: 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,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.



Current Secondary Outcome: 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: 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



Information By: Northwell Health

Dates:
Date Received: May 20, 2011
Date Started: June 2013
Date Completion: January 2018
Last Updated: December 20, 2016
Last Verified: December 2016