Sirolimus for Blood Disorder

Recruiting in Palo Alto (17 mi)

Overseen by Courtney DiNardo, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, Cannabidiol, others

Disqualifiers: Lymphoma, Hematologic malignancies, Myocardial infarction, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

To learn about the safety and effects of low-dose sirolimus in participants with RUNX1-FPD.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect sirolimus levels, such as strong inhibitors or inducers of CYP3A4, and some other specific drugs, at least 7 days before starting the study. If you are on any of these medications, you may need to stop or switch them before participating.

What data supports the effectiveness of the drug Sirolimus for blood disorders?

Sirolimus, known for its use in preventing organ rejection in kidney transplants, has shown effectiveness in reducing acute rejection episodes by over 40% when combined with other drugs. Its properties as an immunosuppressant and its ability to inhibit certain cellular pathways suggest potential benefits for treating various conditions, including blood disorders. ^{1 2 3 4 5}

Is Sirolimus generally safe for humans?

Sirolimus, also known as Rapamune, has been shown to have a favorable safety profile in various conditions, including kidney transplants and skin disorders. However, severe adverse events have been reported during its use for vascular anomalies, indicating that while it is generally safe, there can be serious side effects in some cases. ^{1 2 5 6 7}

How is the drug Sirolimus unique for treating blood disorders?

Sirolimus is unique because it works by inhibiting a specific protein called mTOR, which helps control cell growth and immune response. This mechanism is different from other treatments and makes it effective in reducing immune activity, which is beneficial for conditions involving abnormal immune responses. ^{1 2 3 4 8}

Research Team

Courtney DiNardo, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with RUNX1 Familial Platelet Disorder who have a platelet count of ≥50,000/µL and normal heart, liver, and kidney function can join. They must not have had certain blood disorders or treatments like sirolimus recently and should be free from serious infections or uncontrolled bleeding.

Inclusion Criteria

Participants has provided signed, informed consent before initiation of any study specific procedures

Platelet count of ≥50,000/µL

I am willing to give bone marrow samples at the start and end of my treatment.

Exclusion Criteria

I have not had a blood clot in an artery in the last 6 months.

Known allergy to sirolimus

Total cholesterol >300 mg/dL or triglyceride >400 mg/dL

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-dose sirolimus to evaluate safety and hematopoietic function

22 weeks

2 visits during Week 1, 1 visit during Weeks 2-4, then every 2 weeks until Week 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 weeks

1 visit at Week 24 and 1 visit at Week 52

Treatment Details

Interventions

• Sirolimus (mTOR Inhibitor)

Trial Overview The trial is testing the safety and effects of low-dose Sirolimus on patients with thrombocytopenia due to RUNX1-FPD. Participants will provide bone marrow samples before and after treatment to assess changes in hematopoietic function.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Participants will visit the study clinic 2 times during Week 1, one (1) time during Weeks 2-4, and then 1 time every 2 weeks after that (Weeks 6, 8, 10, and so on) until Week 22 (Month 6). Then participants will have a follow-up visit at Week 24 and again at Week 52 (Month 12). Participants will take sirolimus by mouth every day, at about the same time each day. Swallow the tablet(s) whole with a full glass of water (about 1 cup). Do not crush or chew the tablet(s). Participants may take sirolimus with or without food.

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

🇪🇺 Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

🇨🇦 Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

🇯🇵 Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3107

Patients Recruited

1,813,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Update on transplant pharmacology: sirolimus. [2021] Rapamune (Sirolimus), the latest immunosuppressant agent for solid organ transplants, is prescribed for induction therapy, refractory rejection, steroid withdrawal, and combination therapy. As the use of this agent increases among various transplant populations, it is essential for critical care nurses to be cognizant of the indications, pharmacodynamics, current research findings, side effects, and implications. This knowledge will ultimately improve patient education and outcomes in this ever-growing field of nursing.

2. Canada pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. [2014] Sirolimus, also known as rapamycin (SRL, Rapamune®), was approved in 1999 by the US Food and Drug Administration to prevent graft rejection in renal transplantation. As a member of the mammalian target of rapamycin (mTOR) inhibitor class, its potent immunosuppressant, anti-angiogenic and anti-proliferative properties are well recognized. When compared to other immunosuppressants, SRL has a lower risk of renal, neurologic and lymphoproliferative complications. It has become a promising treatment modality for angiofibromas, Kaposi's sarcoma and other inflammatory and malignant disorders of the skin. With the recent discovery that mTOR inhibitors extend the lifespan of mice, sirolimus and other rapamycin analogs (rapalogs) are emerging as therapeutic targets for the treatment and prevention of age-related diseases.

3. England pubmed.ncbi.nlm.nih.gov

Sirolimus: a comprehensive review. [2019] Sirolimus (Rapamune), Wyeth-Ayerst, Madison, NJ) is a new, potent, immunosuppressant that is emerging as a foundation for long-term immunosuppressive therapy in renal transplantation. The drug acts during both co-stimulatory activation and cytokine-driven pathways via a unique mechanism: inhibition of a multifunctional serine-threonine kinase, mammalian target of rapamycin (mTOR). Although there is no a priori reason to assume it, sirolimus displays a synergistic interaction to enhance the efficacy of cyclosporin A (CsA). In trials wherein the concentrations of CsA and sirolimus were tightly controlled, rates of acute rejection episodes were

4. United States pubmed.ncbi.nlm.nih.gov

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients. [2019] Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone. However, RAPA treatment tends to increase lipid levels, particularly among patients with pre-existing hyperlipidemia.

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Rapamune® (Sirolimus) in kidney transplant recipients: results of a prospective post-marketing surveillance study in Korea. [2019] Few post-marketing surveillance studies have examined the safety and efficacy of Rapamune® (Sirolimus) in Asian countries. This study aimed to better understand safety and efficacy of Rapamune for kidney transplant recipients in the routine clinical practice setting in Korea.

6. Denmark pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune, rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis. [2022] Sirolimus (Rapamune, rapamycin) has been shown to be an effective and safe immunosuppressive drug in adult kidney transplant patients when administered concomitantly with cyclosporine (CsA) and steroids. This study reports on a phase 1 assessment of the drug's tolerance, safety, and pharmacokinetic parameters in pediatric patients. The safety and pharmacokinetic profiles of ascending single doses of sirolimus oral solution were investigated in 32 clinically stable pediatric patients on chronic hemodialysis (n = 26) or peritoneal dialysis (n = 6). Patients were divided into two age groups (5-11 and 12-18 yr), and each patient received either a single dose of sirolimus (1, 3, 9, or 15 mg/m(2)) or placebo. Whole blood and plasma samples were collected from each patient for the determination of sirolimus pharmacokinetic parameters. Safety assessments were based on reports of adverse events and results of scheduled physical examinations, vital sign measurements and clinical laboratory tests. The younger patients (5-11 yr) showed statistically significant increases in whole blood sirolimus t(max) (p

7. United States pubmed.ncbi.nlm.nih.gov

Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. [2022] Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during "off-label use" for vascular anomalies.

8. France pubmed.ncbi.nlm.nih.gov

Dose Escalation Study to Assess the Pharmacokinetic Parameters of a Nano-amorphous Oral Sirolimus Formulation in Healthy Volunteers. [2020] Label="BACKGROUND AND OBJECTIVES" NlmCategory="OBJECTIVE">Sirolimus (Rapamune®) exhibits low bioavailability, high variability and moderate food effect following oral administration. This makes therapeutic blood monitoring of sirolimus concentrations necessary for kidney transplant patients. Furthermore, reaching therapeutic blood sirolimus concentrations in renal cancer patients was found to be challenging when the marketed drug was administered alone. A novel, nano-amorphous formulation of the compound was developed and its pharmacokinetic properties were investigated in a dose escalation study in a first-in-human clinical trial. The effect of food at the highest dose on the pharmacokinetic parameters was also assessed.