Trial Outcomes & Findings for Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy (NCT NCT01869114)

Last Updated: 2025-12-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2025-12-10

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: 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.
Overall Study STARTED	21	28	8
Overall Study COMPLETED	2	4	0
Overall Study NOT COMPLETED	19	24	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: 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.
Overall Study Death	19	18	8
Overall Study Adverse Event/Side Effects/Complications	0	1	0
Overall Study Patient off treatment for other complicating disease	0	1	0
Overall Study Withdrawal by Subject	0	3	0
Overall Study Disease Progression	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Acute Myeloid Leukemia (AML) n=21 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: High Risk Myleodysplastic Syndrome (MDS) n=28 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: MDS or AML With Prior Azacitadine Therapy n=8 Participants 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.	Total n=57 Participants Total of all reporting groups
Sex: Female, Male Female	8 Participants n=4 Participants	9 Participants n=50 Participants	1 Participants n=681 Participants	18 Participants n=639 Participants
Age, Categorical <=18 years	0 Participants n=4 Participants	0 Participants n=50 Participants	0 Participants n=681 Participants	0 Participants n=639 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=4 Participants	4 Participants n=50 Participants	0 Participants n=681 Participants	11 Participants n=639 Participants
Age, Categorical >=65 years	14 Participants n=4 Participants	24 Participants n=50 Participants	8 Participants n=681 Participants	46 Participants n=639 Participants
Sex: Female, Male Male	13 Participants n=4 Participants	19 Participants n=50 Participants	7 Participants n=681 Participants	39 Participants n=639 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=4 Participants	2 Participants n=50 Participants	0 Participants n=681 Participants	2 Participants n=639 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=4 Participants	24 Participants n=50 Participants	8 Participants n=681 Participants	51 Participants n=639 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=4 Participants	2 Participants n=50 Participants	0 Participants n=681 Participants	4 Participants n=639 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=4 Participants	0 Participants n=50 Participants	0 Participants n=681 Participants	0 Participants n=639 Participants
Race (NIH/OMB) Asian	2 Participants n=4 Participants	0 Participants n=50 Participants	0 Participants n=681 Participants	2 Participants n=639 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=4 Participants	1 Participants n=50 Participants	0 Participants n=681 Participants	1 Participants n=639 Participants
Race (NIH/OMB) Black or African American	0 Participants n=4 Participants	5 Participants n=50 Participants	2 Participants n=681 Participants	7 Participants n=639 Participants
Race (NIH/OMB) White	18 Participants n=4 Participants	19 Participants n=50 Participants	6 Participants n=681 Participants	43 Participants n=639 Participants
Race (NIH/OMB) More than one race	0 Participants n=4 Participants	0 Participants n=50 Participants	0 Participants n=681 Participants	0 Participants n=639 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=4 Participants	3 Participants n=50 Participants	0 Participants n=681 Participants	4 Participants n=639 Participants
Region of Enrollment United States	21 participants n=4 Participants	28 participants n=50 Participants	8 participants n=681 Participants	57 participants n=639 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: Arm C was included in the study design, and eight participants were enrolled. However, none of them received study treatment, and no safety or efficacy data were collected. As a result, there is no evaluable data available for this outcome measure, and no data will be available in the future.

Outcome measures

Outcome measures
Measure	Arm A: Acute Myeloid Leukemia (AML) n=21 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: High risk Myleodysplastic Syndrome (MDS) n=28 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: 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.
Number of Participants With Response Progressive Disease (PD)	4 Participants	4 Participants	—
Number of Participants With Response Complete Response (CR)	1 Participants	4 Participants	—
Number of Participants With Response Partial Response (PR)	5 Participants	3 Participants	—
Number of Participants With Response Stable Disease (SD)	13 Participants	6 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: Acute Myeloid Leukemia (AML) n=21 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: High risk Myleodysplastic Syndrome (MDS) n=28 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: 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.
Number of Participants With Adverse Events	20 Participants	11 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: Acute Myeloid Leukemia (AML) n=15 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: High risk Myleodysplastic Syndrome (MDS) n=12 Participants 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: 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.
Mean Percentage of pS6-positive Blasts as Measured by Intracellular Flow Cytometry	18.6 percentage change Interval 4.4 to 49.0	37 percentage change Interval 8.0 to 96.0	—

SECONDARY outcome

Timeframe: Up to day 164

Population: QoL questionnaire score analysis was contingent on demonstrating efficacy in the primary endpoint. The study did not met the primary efficacy endpoint, and QoL assessment was not performed as further data collection for secondary endpoints was not pursued.

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.

Outcome measures

Outcome data not reported

Adverse Events

Arm A: Acute Myeloid Leukemia (AML)

Serious events: 8 serious events

Other events: 20 other events

Deaths: 19 deaths

Arm B: High risk Myleodysplastic Syndrome (MDS)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 18 deaths

Arm C: MDS or AML With Prior Azacitadine Therapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: Acute Myeloid Leukemia (AML) n=21 participants at risk 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. Sirolimus: Given PO Azacitidine: Given IV	Arm B: High risk Myleodysplastic Syndrome (MDS) n=28 participants at risk 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. Sirolimus: Given PO Azacitidine: Given IV	Arm C: MDS or AML With Prior Azacitadine Therapy n=8 participants at risk 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.
General disorders Multi-organ failure	9.5% 2/21 • Number of events 2 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/28 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	9.5% 2/21 • Number of events 2 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/28 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/21 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	3.6% 1/28 • Number of events 1 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.
Infections and infestations Lung infection	4.8% 1/21 • Number of events 1 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/28 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	9.5% 2/21 • Number of events 2 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/28 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.
Infections and infestations Sepsis	4.8% 1/21 • Number of events 1 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/28 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.	0.00% 0/8 • The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as from the first dose of study drug through 30 days after the last dose of study treatment, an average of 7 months. All participant deaths are included in the All-Cause Mortality table. Deaths outside the prespecified AE collection window are excluded from the AE/SAE summary but fully represented in the mortality table.

Other adverse events

Additional Information

Margaret T Kasner, MD

Thomas Jefferson University

Phone: 215-955-3202

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place