Severe Aplastic Anemia (SAA)
Conditions
Keywords
Severe Aplastic Anemia, SAA, Very Severe Aplastic Anemia, vSAA, Romiplostim
Brief summary
Romiplostim has been used in clinical trials for the treatment of severe and very severe aplastic anemia (SAA/vSAA) in Asian participants who are either previously untreated with immunosuppressive therapy (IST) or refractory to IST. This study will evaluate the efficacy of romiplostim in the treatment of participants with SAA/vSAA. The primary objectives of this study are to: Arm 1: Evaluate the efficacy of romiplostim and IST in adult SAA/vSAA participants who are previously untreated with IST (1L) Arm 2: Evaluate the efficacy of romiplostim treatment in adult SAA/vSAA participants who are refractory to IST (2L+)
Interventions
DRUGRomiplostim
Administered as a subcutaneous injection.
DRUGAntithymocyte Globulin
Horse or rabbit antithymocyte globulin administered as an intravenous infusion.
DRUGCyclosporine A
Administered orally.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at time of enrollment * Diagnosis of SAA/vSAA confirmed by blood, bone marrow, and cytogenetic studies * An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening * Arm 1 only: participant requires initial treatment for SAA/vSAA, no matched related donor is available for allogenic hematopoietic cell transplantation (HCT) and will begin IST with antithymocyte globulin and CsA * Arm 2 only: refractory to at least one course of immunosuppressive therapy including horse or rabbit ATG; or ineligible for ATG treatment and refractory to CsA
Exclusion criteria
* Diagnosed as having congenital aplastic anemia (AA) (Fanconi anemia, congenital dyskeratosis, etc) * History of other malignancy within the past 5 years, with exceptions. * Aplastic anemia with hemolytic paroxysmal nocturnal hemoglobinuria (PNH) (hemolytic predominant is defined as lactate dehydrogenase (LDH) \> 1.5 x the upper limit of site normal * Arm 1 only: Previously treated with ATG, CsA, or Alemtuzumab * Previously treated with PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin protein (TPO), romiplostim and other TPO-receptor agonist (eltrombopag, etc) * Patients who are eligible for allogenic HCT and have an available matched related donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1 and 2: proportion of participants achieving any hematologic response at week 14 | Week 14 | Proportion of participants achieving any hematologic response at week 14 based on response criteria: * Platelet response * Erythroid response * Red blood cell count * Hemoglobin concentration * Neutrophil response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1 and 2: number of participants who have a decrease in frequency of platelet and/or red blood cell (RBC) transfusions, or become platelet and/or RBC transfusion independent at week 14 | Week 14 | — |
| Arms 1 and 2: number of participants with serious adverse events | 24 Weeks | — |
| Arms 1 and 2: number of participants with clinically significant changes in laboratory values | 24 Weeks | — |
| Arms 1 and 2: change from baseline in Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) bleeding scale at week 14 | Baseline and Week 14 | The Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto is as follows: 0: No bleeding 1. Petecjoae or mucosal or retinal bleeding that did not require red-cell transfusion 2. Melena, hematemesis, hematuria, or hemoptysis 3. Any bleeding that required red-cell transfusion 4. Retinal bleeding accompanied by visual impairment 5. Nonfatal cerebral bleeding 6. Fatal cerebral bleeding 7. Fatal noncerebral bleeding |
| Arms 1 and 2: serum romiplostim trough concentrations | Prior to romiplostim administration on Weeks 1, 2, 4, 5, 9, 13, and 24 | — |
| Arm 1: number of participants who achieve a complete response (CR) or partial response (PR) at week 14 | Week 14 | — |
| Arms 1 and 2: area under the curve (AUC) of romiplostim | Weeks 1, 2, 4, 5, 9, 13, and 24 | — |
| Arms 1 and 2: time to reach maximum concentration (tmax) of romiplostim | Weeks 1, 2, 4, 5, 9, 13, and 24 | — |
| Arms 1 and 2: half-life (t1/2) of romiplostim | Weeks 1, 2, 4, 5, 9, 13, and 24 | — |
| Arms 1 and 2: number of participant with anti-romiplostim antibodies | Prior to romiplostim administration on Weeks 1 and 13 | — |
| Arms 1 and 2: number of participants with antibodies to thrombopoietin | Prior to romiplostim administration on Weeks 1 and 13 | — |
| Arms 1 and 2: maximum serum concentration (Cmax) of romiplostim | Weeks 1, 2, 4, 5, 9, 13, and 24 | — |
Outcome results
None listed