Clinical research—to advance diagnostics and to develop better treatments—requires patients, but one big challenge in a rare disease such as aplastic anemia is patient recruitment. If patients don’t agree to be “on protocol”, or if only a few enroll, clinical trials fail or take years to reach full accrual. Patients are often surprised to learn that unless they are treated on a research trial, data concerning their outcome is not utilized for research purposes. Also often not appreciated is that even experts with huge clinics rely on carefully conducted and interpreted trials to draw conclusions that are applicable to their own patients. Theoretical assumptions, animal experiments, and anecdotal clinical experiences can help in formulating research and designing a trial, but they do not replace actual clinical results. One recent example in aplastic anemia was our NIH trial, in which Phillip Scheinberg was the principal investigator, that surprisingly showed a major difference in favor of horse anti-thymocyte globulin (ATG) compared to rabbit ATG.
Patients on clinical research protocols often do better than those who receive standard treatments or worse, combinations of treatments devised by an inexperienced doctor. Research usually is carried out in hospitals with large experience in bone marrow failure, which is very valuable in severe disease. Research protocols also provide an opportunity to receive a novel, potentially beneficial therapy. Clinical trials are intended to “advance the field”, and even when not successful they are highly informative to future patients and their doctors as to the choices and their risks and benefits. Participating in research empowers patients and can give them satisfaction in contributing to new developments that may help them but surely will help others.
Recently, our institution completed a pilot study using a novel agent for aplastic anemia called eltrombopag (also known as Promacta®). Eltrombopag is a drug designed to mimic a special protein in the body called thrombopoietin (TPO). Like naturally occurring TPO, eltrombopag causes the body to make more platelets. Eltrombopag has been approved by the U.S. Food and Drug Administration (FDA) to treat low blood platelet counts in adults with chronic ITP (immune thrombocytopenic purpura). Eltrombopag may also cause the body to make more red and white blood cells.
In a trial performed at the NIH where patients with severe aplastic anemia who failed to respond to prior immunosuppressive therapy were subsequently treated with eltrombopag, 44% showed an improvement in their blood counts. These results indicated that eltrombopag may be useful when given in addition to standard treatment for severe aplastic anemia. Laboratory studies suggest that eltrombopag may stimulate hematopoietic stem cells, not just the cells that make platelets, which is a very exciting scientific finding and may represent a major advance in the approach to bone marrow failure. We at NIH are conducting a clinical trial, administering eltrombopag to patients at the start of their disease (clinicaltrials.gov, NCT01623167). The purpose of this study is to evaluate the usefulness of the addition of eltrombopag to standard immunosuppressive therapy (horse ATG and cyclosporine) in study participants who have severe aplastic anemia and have not previously been treated with immunosuppressive therapy. This research should help us determine the best first line therapy for patients with aplastic anemia.