Phase 2
N=136
Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia
Immunosuppresion · Thrombocytopenia · Pancytopenia · Neutropenia
Bottom Line
View on ClinicalTrials.gov: NCT00260689 ↗Enrolled (actual)
136
Serious AEs
17.7%
Results posted
Jun 2017
Primary outcome: Primary: Hematologic Response — 38; 20; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Anti-thymocyte globulin (rabbit) (Biological); Anti-thymocyte globulin (horse) (Biological); Cyclosporine (Drug); Alemtuzumab (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- May 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Hematologic Response |
40; 18; 2 | — |
| PRIMARY Hematologic Response |
40; 18; 2 | — |
| PRIMARY Hematologic Response |
40; 18; 2 | — |
Summary
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation offers the opportunity for cure in 70% of patients, but most patients are not suitable candidates for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a histocompatible donor. For these patients, comparable long term survival is attainable with immunosuppressive treatment with anti-thymocyte globulin (ATG) and cyclosporine (CsA). However, of those patients treated with horse ATG(h-ATG)/CsA, one quarter to one third will not respond, and about 50% of responders relapse. Auto-reactive T cells may be resistant to the effect of ATG/CsA (non-responders), while in others residual auto-reactive T cells expand post-treatment, leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). As long term survival is correlated to response rates and robustness of hematopoietic recovery, novel immunosuppressive regimens that can achieve hematologic response and decrease relapse rates are needed.
This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint, as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution. Randomization is employed to obtain an equal distribution of subject to each arm; comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms (rabbit-ATG [r-ATG] versus standard h-ATG; alemtuzumab vs standard h-ATG). For long course CSA, comparison of primary end points will be to well established historic relapse rate of 38% at 2-3 years and a cumulative rate of clonal evolution of 15%.
Eligibility Criteria
-INCLUSION CRITERIA:
- Severe aplastic anemia characterized by bone marrow cellularity less than 30% (excluding lymphocytes) and at least two of the following:
- Absolute neutrophil count less than 500/microliter
- Platelet count less than 20,000/microliter
- Absolute reticulocyte count less than 60,000/microliter
- Age greater than or equal to 2 years old
- Weight greater than 12 kg
EXCLUSION CRITERIA
- Diagnosis of Fanconi's anemia
- Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia (ANC less than 200/microliter) will not be excluded initially if cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the patient will go off study.
- Prior immunosuppressive therapy with ATG, ALG, alemtuzumab, or high dose cyclophosphamide.
- Infection not adequately responding to appropriate therapy.
- Serologic evidence of HIV infection.
- Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old Man's Beard) within 2 weeks of enrollment.
- 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.
- Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible.
- Current pregnancy, or unwillingness to take oral contraceptives or refrain from pregnancy if of childbearing potential.
- Not able to understand the investigational nature of the study or give informed consent.
Data sourced from ClinicalTrials.gov (NCT00260689). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.