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

Sponsor

Northwell Health (Other)

Overall Status

Unknown status

CT.gov ID

NCT01362595

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diamond Blackfan Anemia Blackfan Diamond Syndrome DBA Congenital Hypoplastic Anemia Pure Red Cell Aplasia	Drug: leucine	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia

Actual Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Jun 30, 2018

Anticipated Study Completion Date :

Apr 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Leucine No alternative treatment arm	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 Names: L-leucine

Arm

Intervention/Treatment

Other: Leucine

No alternative treatment arm

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 Names:

L-leucine

Outcome Measures

Primary Outcome Measures

Response to Leucine in Transfusion dependent patients with Diamond Blackfan Anemia [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: 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

Secondary Outcome Measures

Side effects of leucine in transfusion-dependent DBA patients [Total study 12-15 months]
Secondary outcomes include safety parameters such as type, frequency, and severity of adverse events and relationship to leucine.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Stanford University Medical Center	Palo Alto	California	United States	94304
3	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	University of Louisville	Louisville	Kentucky	United States	40202
5	Boston Children's Hospital	Boston	Massachusetts	United States	02115
6	University of Michigan C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
7	University of Missouri-Columbia Women's and Children's Hospital	Columbia	Missouri	United States	65201
8	Children's Specialty Center of Nevada	Las Vegas	Nevada	United States	89109
9	Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	UT Southwestern Medical Center	Dallas	Texas	United States	75390