Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy

• Register: ClinicalTrials.gov
• Last refreshed on: 15 April 2024
• Main ID: NCT02979873
• Date of registration: 01/12/2016
• Prospective Registration: Yes
• Primary sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Public title: Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy
• Scientific title: A Randomized Trial of Sirolimus (Rapamune(R)) for Relapse Prevention in Patients With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy
• Date of first enrolment: December 19, 2016
• Target sample size: 118
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02979873
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Bhavisha A Patel, M.D.
• Affiliation: National Heart, Lung, and Blood Institute (NHLBI)

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

• Name: Ivana Darden, R.N.

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

1. Age greater than or equal to 2 years old

2. Weight greater than 12 kg

3. Previous diagnosis of SAA by bone marrow biopsy and cytogenetics, treated with
lymphodepleting therapy ATG, cyclophosphamide or alemtuzumab that included
cyclosporine. The lymphodepleting therapy must have been administered at least 12
months prior.

4. Continuous treatment with cyclosporine for the previous 6 months (excluding minor
dose delays not exceeding more than 30 days).

5. Evidence of a hematologic response to an lymphodepletion-based regimen as
evidence of at least two of the following:

- Absolute neutrophil count greater than or equal to 500/uL

- Platelet count greater than or equal to 20,000/uL (without transfusion support)

- Absolute reticulocyte count greater than or equal to 60,000/uL (or hemoglobin 10 gm/dL
without transfusion support)

EXCLUSION CRITERIA:

1. Evidence of relapse of aplastic anemia due to cyclosporine withdrawal during the
previous 6 months

2. Prior use of sirolimus or other mTOR inhibitor within 12 weeks of study entry

3. Myelodysplastic syndrome or acute myeloid leukemia, according to WHO diagnostic
criteria (if baseline BM consistent with MDS after enrollment, patients will be
considered ineligible and immediately exit the study, and the subject can be replaced
with another subject)

4. Patients that are on CYP3A4 inhibitors and cannot replace these medications with other
equivalent medications for the period of study: protease inhibitors (ritonavir,
indinavir, nelfinavir, saquinavir), some macrolide antibiotics (clarithromycin,
telithromycin, erythromycin), azole anti-fungals (fluconazole, itraconazole,
ketoconazole), metroclopramide, felodipine, nifedipine, carbamazepine, phenobarbital,
grapefruit juice and St. John s Wort.

5. Anaphylactic or hypersensitivity reaction to sirolimus

6. Patients with infections not adequately responding to appropriate therapy as evidenced
by persistence of a clear source of infection that, in the view of the investigator,
would preclude safe treatment with sirolimus.

7. Current pregnancy, or unwillingness to take oral contraceptives or use the barrier
methods of birth control or practice abstinence to refrain from pregnancy if of
childbearing potential during the course of the study 8. Lactating women, due to the
potentially harmful effects on the nursing child.

9. Patients who have received live vaccines within the past 30 days

10. Patients with cancer who are actively receiving chemotherapeutic treatment or who take
drugs with hematological effects such as thrombopoietin receptor agonists (such as
eltrombopag), granulocyte-colony stimulating factor or erythroid stimulating agents.

11. Moribund status such that death within 7 to 10 days is likely. Comorbidities of such
severity that in the view of the Investigator it would likely preclude the patient's
ability to tolerate sirolimus.

12. Inability to understand the investigational nature of the study or to give informed
consent or without a legally authorized representative or surrogate that can provide
informed consent.



Age minimum: 2 Years
Age maximum: 99 Years
Gender: All

Health Condition(s) or Problem(s) studied

Severe Aplastic Anemia

Intervention(s)

Drug: Sirolimus

Primary Outcome(s)

To determine if the rate of relapse at 24 months after CSA discontinuation can be improved by conversion to sirolimus in severe aplastic anemia patients who have responded to IST. [Time Frame: 24 months]

Secondary Outcome(s)

Safety and tolerability of sirolimus. [Time Frame: 3 mo]

Secondary ID(s)

17-H-0019

170019

Source(s) of Monetary Support

Please refer to primary and secondary sponsors