‘An Open-Label, Single-Arm Interventional Study to Evaluate the Safety and Efficacy of Romiplostim in Danazol Resistant/ Intolerant Inherited Bone Marrow Failure Syndromes’

This interventional pilot study proposes to evaluate the efficacy and safety of repurposed drug Romiplostim in children with inherited bone marrow failure syndromes (IBMFS), namely Fanconi anemia and Dyskeratosis Congenita who are Danazol resistant/ intolerant and are pancytopenic as a non-transplant medical therapy in patients who are transplant ineligible or do not have HLA matched related or unrelated donor.

Primary Objective: To study the effectiveness of romiplostim to reduce transfusion requirement or improve bone marrow cellularity in patients with IBMFs at week 24 of therapy.

Secondary Objectives: 1. To monitor for adverse events in use of Romiplostim for patients with IBMFS 2. To evaluate the effectiveness of Romiplostim in achieving transfusion independence in patients with IBMFS at week 24 of therapy 3. To identify the genetic mutations seen in patients with Danazol resistant IBMFS.

Primary endpoint: To evaluate efficacy of the drug defined as any one or more of following primary responses. A. Twenty Five percent reduction in transfusion requirement compared to baseline or B. Achieving platelet count more than 30,000 per microlitre, Hb more than  8 gram per decilitre or ANC more than  500 per microlitre  or C. Transfusion independence for 4 consecutive weeks or D. Bone marrow response, defined as an increase in bone marrow cellularity by at least two-fold from baseline at either of time points of assessment (Week 12 in patients with no hematological response & week 24 in all patients).

Secondary Endpoints: 1. To evaluate drug related and disease related adverse events 2. To evaluate the percentage of study participants who achieve transfusion independence during the study period. 3.To identify the genetic mutations seen in patients with Danazol resistant IBMFS.

Sample size is 10 participants with danazol resistant / intolerant IBFMS.

Study Subjects: Children between the age of 2 to 18 years (inclusive of 2 years and 18 years).

Study site: Madras Medical College

Children with Danazol resistant/ intolerant IBMFS will undergo baseline marrow evaluation to rule out Myelodysplastic syndromes. They will also undergo genetic studies to identify disease causing mutation. Children fulfilling eligibility criteria and after informed consent, will be administered study drug Inj Romiplostim initially at dose of 3mcg/kg/week subcutaneously (week 1) and escalated every week by 1 mcg/kg/week (week 8) to reach a ceiling dose of 10 mcg/kg/week and continued in that dose till week 12. Their response to therapy will be monitored with weekly blood counts and any adverse events will be monitored. The study duration is 36 months .