Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

November 18, 2025 updated by: Sidney Kimmel Cancer Center at Thomas Jefferson University

A Phase II Study of Azacitidine and Sirolimus for the Treatment of High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Refractory to or Not Eligible for Intensive Chemotherapy

This phase II trial studies how well sirolimus and azacitidine works in treating patients with high-risk myelodysplastic syndrome or recurrent acute myeloid leukemia. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sirolimus and azacitidine may kill more cancer cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To characterize the rate of response to azacitidine and sirolimus in adults with high-risk myelodysplastic syndrome (MDS), or relapsed or refractory acute myeloid leukemia (AML) or those unable or unwilling to tolerate high dose chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the pharmacodynamic effect of sirolimus on inhibition of mammalian target of rapamycin (mTOR) signaling in adults with high-risk MDS, or relapsed or refractory AML or those unable or unwilling to tolerate high dose chemotherapy.

II. To determine the safety and tolerability of sirolimus and azacitidine in adults with high-risk MDS, or relapsed or refractory AML or those unable or unwilling to tolerate high dose chemotherapy.

III. To determine the progression free survival and overall survival in adults with high-risk MDS, or relapsed or refractory AML or those unable or unwilling to tolerate high dose chemotherapy.

IV. To determine if the quality of life of patients is improved with the combination of azacitidine and sirolimus when compared to historical controls of azacitidine alone.

OUTLINE:

Patients receive sirolimus orally (PO) on days 1-10 or 1-12 and azacitidine intravenously (IV) on days 4-8, 11, and 12 or days 4-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Sewell, New Jersey, United States, 08012
        • Jefferson Health NJ Division (Kennedy Hospital)
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Hospital - Jefferson Health
      • Philadelphia, Pennsylvania, United States, 19124
        • Jefferson Health, Aria Hospital
      • Philadelphia, Pennsylvania, United States, 19148
        • Jefferson Health, Methodist Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients must have a diagnosis of one of the following:

    • MDS (Arm A): High-risk MDS defined as: >5% blasts in bone marrow and/or the following cytogenetic categories: presence of inv(3)/t(3q)/del(3q), -7/del(7q), complex cytogenetics (3 or more abnormalities)
    • AML (Arm B): Relapsed/refractory/unable to tolerate conventional chemotherapy
    • MDS or AML as above BUT with prior therapy with Azacitibine (Arm C): Patients who meet criteria for either Arm A or Arm B but have been treated or are currently treated with Azacitibine *Note: As of July 2018, only high risk MDS patients will be eligible as Arm B is closed. As of October 2017, those patients with MDS who have received prior treatment will now be enrolled in Arm A as Arm C is closed.
  2. Patients must be ≥ 18 years old
  3. Patients must have an ECOG performance status of <= 2 (see Attachment 1).
  4. Patients must have a life expectancy of at least 4 weeks.
  5. Patients must be able to consume oral medication.
  6. Patients must have completed any radiotherapy four weeks prior to study entry, 0-2 weeks for local palliative XRT (small port).
  7. Patients must have recovered from the toxic effects of any prior chemotherapy to < Grade 2 (except for alopecia).
  8. Required initial laboratory values: Creatinine≤ 2.0mg/dL; total or direct bilirubin ≤ 1.5mg/dL (if not due to the leukemia itself or known Gilbert's Syndrome);(as documented by treating physician) SGPT(ALT) ≤ 3xULN; glucose <200 mg/dL, negative pregnancy test for women of child-bearing potential.
  9. Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
  10. Patients may have had a prior stem cell transplant (autologous or allogeneic), however they may not have active GvHD, nor be on any immunosuppression

Exclusion Criteria:

  1. Patients must not be receiving any chemotherapy agents (except Hydroxyurea)

    • Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
    • Patients can not have received more than 3 prior lines of therapy for their hematologic malignancy. Patient may have previously had azacitidine or decitabine will be eligible to enroll on Arm A (MDS)
  2. Patients must not be receiving growth factors.
  3. Patients with a current second malignancy requiring systemic therapy, other than non-melanoma skin cancers, are not eligible. If a patient has had a prior second malignancy that is not currently requiring active treatment, the patient will be considered eligible.
  4. Patients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.

  5. Patients may not take any of the following medications while on study, but will be considered eligible if medication is discontinued 72 hrs prior to first dose of Sirolimus:

    • Carbamazepine (e.g. Tegretol)
    • Rifabutin (e.g. Mycobutin)
    • Rifampin (e.g. Rifadin)
    • Rifapentine (e.g. Priftin)
    • St. John's Wort- may decrease effects of sirolimus by decreasing the amount of sirolimus in the body
    • Clarithromycin (e.g. Biaxin)
    • Cyclosporin e.g. (Neoral or Sandimmune)
    • Diltiazem (e.g. Cardizem)
    • Erythromycin (e.g. Akne-Mycin, Ery-Tab)
    • Itraconazole (e.g. Sporanox)
    • Fluconazole (e.g. Diflucan)
    • Ketoconazole (e.g. Nizoral)
    • Telithromycin (e.g. Ketek)
    • Verapamil (e.g. Calan SR, Isoptin, Verelan)
    • Voriconazole (e.g. VFEND) - May increase the effects of sirolimus by increasing the amount of this medicine in the body. Can take 72 hours after last dose of Sirolimus
    • Tacrolimus (e.g. Prograf) - May cause liver transplant rejection or serious side effects in patients on sirolimus.
  6. Patients with known HIV positivity or AIDS-related illness are not eligible.
  7. Patients with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.
  8. Patients must not have received any investigational agents within 21days of study entry.
  9. Patients must not be pregnant or breastfeeding. Pregnancy tests must be obtained for all females of child-bearing potential. Pregnant or lactating patients are ineligible for this study due to the unknown human fetal or teratogenic toxicities of rapamycin. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
  10. Patients who have uncontrolled infection are not eligible. Patients must have any active infections under control. Fungal disease must be stable for at least 2 weeks before study entry. Patients with bacteremia must have documented negative blood cultures prior to study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High risk Myleodysplastic Syndrome (MDS)
Patients receive sirolimus PO on days 1-10 or 1-12 and azacitidine IV on days 4-8, 11, and 12 or days 4-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Sirolimus
Given PO
Other Names:
  • Rapamune
  • rapamycin
Drug: Azacitidine
Given IV
Other Names:
  • Vidaza
  • 5-azacytidine
Experimental: Acute Myeloid Leukemia (AML)
Patients receive sirolimus PO on days 1-10 or 1-12 and azacitidine IV on days 4-8, 11, and 12 or days 4-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Sirolimus
Given PO
Other Names:
  • Rapamune
  • rapamycin
Drug: Azacitidine
Given IV
Other Names:
  • Vidaza
  • 5-azacytidine
Experimental: MDS or AML with prior Azacitadine therapy
Patients receive sirolimus PO on days 1-10 or 1-12 and azacitidine IV on days 4-8, 11, and 12 or days 4-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Sirolimus
Given PO
Other Names:
  • Rapamune
  • rapamycin
Drug: Azacitidine
Given IV
Other Names:
  • Vidaza
  • 5-azacytidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Response
Time Frame: Up to 5 years

MDS: Patients meeting an erythroid response, a platelet response, or a neutrophil response will be considered responders.

AML: Patients achieving a complete remission (CR), complete response in the absence of a total platelet recovery (CRp), or partial remission (PR) will be considered responders.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: From the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months
Adverse events will be assessed and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. All AEs will be recorded and summarized by frequency and severity.
From the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months
Mean Percentage of pS6-positive Blasts as Measured by Intracellular Flow Cytometry
Time Frame: Up to day 4 before azacitidine administration
The mean percentage of pS6-positive blasts in bone marrow samples was measured using intracellular flow cytometry before and after sirolimus administration. A reduction in pS6-positive blasts indicates inhibition of mTOR signaling. Results are reported as mean values along with the corresponding range.
Up to day 4 before azacitidine administration
Quality of Life (QOL) Assessed by the European Organization for Research and Treatment of Cancer (EORTC) QOL and the Mental Health Inventory (MHI)
Time Frame: Up to day 164
EORTC QOL a 30-item questionnaire covering functional scales, symptom scales, and a global health status/QOL scale. MHI is a validated patient-reported outcome instrument used to assess psychological well-being across multiple domains. Participants rate items on a 6-point Likert scale. Scores are transformed to a 0-100 scale, with higher scores indicated better mental health.
Up to day 164

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

  • Principal Investigator: Margaret Kasner, MD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 8, 2013

Primary Completion (Actual)

January 3, 2024

Study Completion (Actual)

January 3, 2024

Study Registration Dates

First Submitted

May 28, 2013

First Submitted That Met QC Criteria

May 30, 2013

First Posted (Estimated)

June 5, 2013

Study Record Updates

Last Update Posted (Estimated)

December 10, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12D.587
  • 2012-50 (CCRRC)
  • JT 3016 (Other Identifier: JeffTrial Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Recurrent Adult Acute Myeloid Leukemia

Clinical Trials on Sirolimus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe