Recruiting
Phase 1
Phase 2

Sirolimus & Cyclosporine

Sponsor:

Office of Rare Diseases (ORD)

Code:

NCT00319878

Conditions

Anemia, Aplastic

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Interventions

Sirolimus

Cyclosporine

Study Details

Brief summary:

Aplastic anemia is a rare autoimmune disorder in which the bone marrow production of blood cells is greatly decreased or absent. Symptoms include fatigue, weakness, tiny reddish-purple marks on the skin, abnormal bruising, and bleeding from the gums, nose, or intestine. While some cases of aplastic anemia are caused by medications, toxic exposures, or inherited genes, most often the cause remains unknown. The purpose of this study is to determine the safety and efficacy of combining two drugs, sirolimus and cyclosporine, for treating individuals with aplastic anemia that has not responded to other treatments.

Conditions

Anemia, Aplastic

Study ID

NCT00319878

Start date

May, 2006

Status verified date

Oct, 2008

Completion date

Dec, 2009

Anticipated

Primary completion date

Jul, 2009

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Diagnosis of moderate or severe aplastic anemia with bone marrow cellularity of less than 25%
  • Falls within one of the following descriptions at the time of the original diagnosis:

1. For severe aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 500/uL; absolute reticulocyte count less than 60,000/uL; and platelet count less than 20,000/uL
2. For moderate aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 1200/ul; hemoglobin less than 8 g/dL with corrected reticulocyte count less than 1%; and platelet count less than 60,000/uL (Note: Participants who have progressed from moderate to severe aplastic anemia prior to study entry will be classified as having severe aplastic anemia)
  • Diagnosis of refractory aplastic anemia, as defined by a failure to achieve at least a partial response to ATG within 6 months of treatment. Individuals who had a prior response to ATG but who have relapsed and not responded to salvage ATG are eligible. Individuals with relapsed disease who are not candidates for salvage ATG because they experienced a serious or life-threatening complication prior to ATG are also eligible.
  • A Karnofsky performance status of at least 60%
  • Adequate organ function, as defined by creatine levels less than 1.5 times the upper limit normal (ULN), and liver function tests (AST, bilirubin) less than 2 times the ULN
  • Women of childbearing age must be willing to use effective contraception throughout the study

Exclusion Criteria:

  • Received ATG treatment less than 6 months prior to study entry
  • Candidate for related allogeneic stem cell transplantation
  • Active uncontrolled infection
  • History of myelodysplastic syndrome or bone marrow cytogenetic abnormalities
  • History of Fanconi's anemia or other congenital form of aplastic anemia
  • Treatment with an investigational agent within 1 month of study entry
  • HIV infection
  • Pregnant or breastfeeding

Study Design

Enrollment

52 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1

Participants will be treated with sirolimus and cyclosporine. In phase I, each dose cohort will initially enroll three patients. If no dose-limiting toxicity (DLT) is observed by Day 28 in any patient of a cohort, then 3 patients will be treated with the next highest sirolimus dose. If 1 out of 3 patients in any cohort experiences a DLT, then 3 more patients will be enrolled in that cohort. If no more patients have a DLT by Day 28, then sirolimus dose escalation will proceed. If one or more patients experience a DLT then that dose level will be considered to be the maximum tolerated sirolimus dose, and Phase II patients will be treated at the next lowest level. Cyclosporine will be given as a twice daily oral dose.

Interventions

Sirolimus

Oral loading dose followed by a once daily dose:

  • Cohort 1: Loading Dose - 1.2 mg; Daily Dose - 0.4 mg
  • Cohort 2: % Dose Increase - 100%; Loading Dose - 2.4 mg; Daily Dose - 0.8 mg
  • Cohort 3: % Dose Increase - 67%; Loading Dose - 3.9 mg; Daily Dose - 1.3 mg
  • Cohort 4: % Dose Increase - 50%; Loading Dose - 6.0 mg; Daily Dose - 2.0 mg

Cyclosporine

Dose of 5 mg/kg divided as a twice daily oral dose

Primary outcome measure

  • Safety and tolerability of sirolimus and cyclosporine in each stratum of participants [ Time Frame: Measured at Month 6 ]

Central Contacts and Locations

Central contacts

Lynn Tihopu

310-794-0738

Meenal Chalukya

310-825-8091

Locations

UCLA Center for Health Sciences

Recruiting

Los Angeles, California, United States, 90095

Contacts

Ronald Paquette, MD

310-206-5755paquette@ucla.edu

Principal Investigator:

Ronald Paquette, MD

Lee Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33606

Principal Investigator:

Alan List, MD

Taussig Cancer Center, Cleveland Clinic Foundation

Recruiting

Cleveland, Ohio, United States, 44195

Principal Investigator:

Jaroslaw P. Maciejewski, MD

Penn State University Cancer Center

Recruiting

Hershey, Pennsylvania, United States, 17033

Principal Investigator:

Thomas Loughran, MD

More Information

Sponsor

Office of Rare Diseases (ORD)

Last update posted

Oct 7, 2008

Last verified

Oct, 2008

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Office of Rare Diseases (ORD) on 2008-10-07.