Phase 2
N=1
A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
Aplastic Anemia · Neutropenia · Pancytopenia · Severe Aplastic Anemia
Bottom Line
View on ClinicalTrials.gov: NCT01187017 ↗Enrolled (actual)
1
Serious AEs
100.0%
Results posted
Mar 2016
Primary outcome: Primary: Response Rate at 6 Months — 1; 0; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cyclophosphamide (Drug); Fludarabine (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- Jul 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Response Rate at 6 Months |
1; 0; 0 | — |
| SECONDARY Number of Participants With Hematologic Response |
0; 0; 1 | — |
| SECONDARY Number of Patients Who Experienced Disease Relapse |
— | — |
| SECONDARY Number of Participants With Clonal Evolution |
— | — |
| SECONDARY Participant Survival Following Fludarabine/ Cyclophosphamide in Participants With Severe Aplastic Anemia |
1 | — |
Summary
Background:
* Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in low blood cell counts, which require frequent transfusions. Standard initial treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). Patients with SAA who do not respond to initial treatment with ATG (refractory) have a high risk of dying without additional treatment. In these cases, for those who do not have a matched bone marrow transplant donor there is no well-defined standard therapy. In our experience with patients who do not respond to horse ATG + CsA, only about one-third of patients who are re-treated with rabbit ATG + CsA improve. Experience with cyclophosphamide in the treatment of refractory severe aplastic anemia suggests that this drug is able to improve blood counts in about 50% of cases. However, the cyclophosphamide regimen has been associated with a significant infection risk (mostly caused by fungus) in studies conducted over 10 years ago due to the lowering of the white blood cell levels.
* Better antibiotic drugs against fungus have been developed and are widely used to treat patients who have low white blood cell counts and are at risk of developing infections. In SAA patients in particular, these newer antibiotics have had a large impact in preventing and treating fungus infections. Researchers are revisiting the use of cyclophosphamide at lower doses to minimize its side effects given in combination with another immune suppressant, fludarabine.
Objectives:
- To determine the safety and effectiveness of the combination of fludarabine plus cyclophosphamide in treating severe aplastic anemia that has not responded to initial treatments.
Eligibility Criteria
-INCLUSION CRITERIA:
- Severe aplastic anemia characterized by:
Bone marrow cellularity < 30 percent (excluding lymphocytes)
AND
At least two of the following:
- Absolute neutrophil count < 500/ microL
- Platelet count < 20,000/ microL
- Absolute reticulocyte count < 60,000/ microL
- Failure to respond to an initial course of h-ATG/CsA at least 3 months post-treatment or a suboptimal response to initial h-ATG/CsA defined by both platelet and reticulocyte count < 50,000 /microL at 3 months post-treatment
OR
- Refractory SAA unresponsive to both horse and rabbit ATG-based regimens
- Age greater than or equal to 2 years old
- Weight greater than or equal to 12 kg
EXCLUSION CRITERIA
- Diagnosis of Fanconi anemia
- Cardiac ejection fraction < 30 percent (evaluated by ECHO)
- Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with the presence of trisomy 8, loss of Y or del(20q) will not be excluded in the absence of dysplastic changes in the marrow. Patients with very severe neutropenia (ANC < 200 /microL) 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 high dose Cy
- Infection not adequately controlled with appropriate therapy
- Serologic evidence of HIV infection
- 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 30 days is likely
- Subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects
- 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 to give informed consent
Data sourced from ClinicalTrials.gov (NCT01187017). 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.