Aplastic Anemia
Conditions
Keywords
Aplastic Anemia
Brief summary
This Phase II open-label interventional clinical trial aims to evaluate the efficacy of romiplostim, in patients with severe aplastic anemia (SAA), both treatment naïve and relapsed/refractory, in inducing trilineage hematopoiesis in children and young adults.
Detailed description
The study is designed as a Phase II, multicenter, investigator-initiated, open label, interventional study that will recruit children (age: \>2 to \<21 years) with SAA. The primary objective of the study is to evaluate the efficacy of romiplostim (a TPO-RA with an orphan drug designation) for the treatment of SAA in children and young adults with newly diagnosed and relapsed or refractory SAA. Hematologic complete response (HCR) will be used to assess the therapy response.
Interventions
DRUGRomiplostim
The investigational drug, Romiplostim, is a thrombopoietin receptor agonist (TPO-RA) that has been granted orphan drug designation by the FDA.
Standard of Care immunosuppressive therapy (IST) includes HORSE ANTI-THYMOCYTE GLOBULIN (H-ATG) and Cyclosporine (CSA)
Sponsors
Department of Health and Human Services
Food and Drug Administration (FDA)
Anjali Sharathkumar
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Age ≥2 years to ≤21 years * Child should be receiving ongoing care with pediatric hematology/oncology provider. * Confirmed Diagnosis of SAA and other related conditions based on following criteria. Diagnosis of severe Aplastic anemia (newly diagnosed or refractory based on history of prior treatments) is established if bone marrow cellularity \<25% to 30% and at least two of the following criteria are met: (a) absolute neutrophil count \<0.5 × 10\^9 /L, (b) platelet count \<20 × 10\^9/L, and (c) hemoglobin \<8 g/dL. In the event bone marrow cellularity is \>30% but patient presents with severe pancytopenia and its complications; the diagnosis of SAA will be considered at the discretion of PI. For relapsed or refractory AA, minor variations in hematological parameters will be acceptable, e.g., platelet count of \<50 x 10\^9/L or hemoglobin of ≤9 g/dL. OR Diagnosis of refractory aplastic anemia will include a confirmed diagnosis of SAA and the clinical assessment by the treating physician that the patient has not responded to the frontline IST by 6 months. OR Diagnosis of relapsed aplastic anemia will be determined by previous diagnosis of SAA and the prior history of successful hematologic response to IST with subsequent loss of response and/or requirement of supportive therapy\*. \*Adequate organ function within 7 days of enrollment defined as: Creatinine: ≤2.0 mg/dL Hepatic function: Elevation of liver enzymes is acceptable for patients with hepatitis-induced SAA if patient does not have history of chronic liver problem such as liver cirrhosis. If necessary, liver biopsy will be performed. * Females of childbearing potential agree to use effective contraception during the study period and for 4 months after completion of therapy. * Patient with available allogenic stem cell donor chooses to defer HSCT option at least for 12-weeks. * Parent, guardian, or patient (if \>18 years of old) must be able to provide written and voluntary informed consent and assent (if \>12 years of age).
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: * Age \< 2 years or \>21 years \*Availability of suitable HLA-matched related or HLA-matched unrelated (9/10 or 10/10) allogenic stem cell donor and the participant fulfills the requirement for HSCT and opts to undergo allogenic HSCT.\*\* * Patients with Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones \>50% of granulocytes or RBC at time of enrollment. * Preexisting condition with predisposition for thrombosis such as protein C, S, antithrombin deficiency, homozygous factor V Leiden or prothrombin 20210 polymorphism, history of idiopathic thromboembolism with patient or first degree relative. * Diagnosis of bone marrow failure syndrome with cancer predisposition, including chromosomal fragility disorders (Fanconi anemia, Bloom syndrome, Ataxia Telangiectasia) and other conditions with known association towards cancer predisposition.# * Presence of complex karyotype or monosomy 7 or 5q- or other cytogenetic abnormality with known predisposition to cancer. * Diagnosis of MDS. * Patients taking concurrent therapy with eltrombopag, avatrombopag, and lusutrombopag\*\*\*. * Patients taking concurrent therapy with androgens\*\*\*. * Females who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin \[β-hCG\] pregnancy test) at screening or pre-dose on Day 1. * Current alcohol or drug abuse. * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. * Active and uncontrolled infections (e.g., sepsis, hepatitis B, hepatitis C). * Chronic liver disease, i.e., fibrosis or cirrhosis. * Patients infected with Human Immunodeficiency Virus (HIV). * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to romiplostim that contraindicates the patient's participation. * Known history of sensitivity or allergy to the active substance, to any of the excipients, or to any E. coli-derived product. * Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 7-10 days is likely. * Current pregnancy or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during this study. * Inability to understand investigational nature of the study or give informed consent. \# Clarification about
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of romiplostim added to Immunosuppressive therapy (IST) as measured by the hematologic complete response rate (HCRR) at Week 24 | During 24 weeks of therapy | Proportion of participants with hematopoietic complete response at 24 weeks defined as hemoglobin ≥10 g/dL, ANC ≥1 x 10\^9/L, and platelet count ≥100 x 10\^9/L without having received transfusion of packed red blood cells within the last 6 weeks or platelets or G-CSF/GM-CSF within the last 2 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events as assessed by CTCAE v5.0 | One year following completion of treatment | To further characterize the safety profile |
| Proportion of participants with a new cytogenetic abnormality | One year following completion of treatment | For safety the proportion of participants with a new cytogenetic abnormality (e.g., paroxysmal nocturnal hemoglobinuria (PNH), acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), thrombocytosis, and bone marrow fibrosis). |
Countries
United States
Contacts
Primary ContactAnjali Sharathkumar, MD
Outcome results
None listed