Recurrent Adult Acute Myeloid LeukemiaPhase 2NCT02583893
Biomarkers in Predicting Treatment Response to Sirolimus and Chemotherapy in Patients With High-Risk Acute Myeloid Leukemia
A Phase 2 study testing Sirolimus, Mitoxantrone and Etoposide in people with Recurrent Adult Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial summary
This pilot phase II trial studies whether biomarkers (biological molecules) in bone marrow samples can predict treatment response to sirolimus and chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) in patients with acute myeloid leukemia (AML) that is likely to come back or spread (high-risk). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia
- What is being tested?
- Sirolimus, Mitoxantrone and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2015to 17 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:
- Primary refractory non-M3 AML
- Residual leukemia after a minimum of 2 prior courses of chemotherapy (Same or different)
- Evidence of leukemia recurrence after a nadir bone marrow biopsy demonstrates no evidence of residual leukemia.
- Evidence of leukemia after induction therapy which, in the opinion of the investigator, would be appropriate for reinduction with sirolimus/MEC therapy.
- Relapsed non-M3 AML
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- Previously untreated non-M3 AML age >60 with no evidence of favorable karyotype defined by presence of t(8;21)(q22;q22) [AML1-ETO], inv16(p13;q22), or t(16;16)(p13;q22) [CBFβ;MYH11] by cytogenetics, FISH, or RT-PCR
- Previously untreated secondary AML (from antecedent hematologic malignancy or following therapy with radiation or chemotherapy for another disease) with no evidence of favorable karyotype defined by presence of t(8;21)(q22;q22) [AML1-ETO], inv16(p13;q22), or t(16;16)(p13;q22) [CBFβ;MYH11] by cytogenetics, FISH, or RT-PCR
- Subjects must be ≥ 18 years of age.
- Subjects must have an ECOG performance status of 2 or less (see Appendix1).
- Subjects must have a life expectancy of at least 4 weeks.
- Subjects must be able to consume oral medication.
- Subjects must have recovered from the toxic effects of any prior chemotherapy to =< Grade 1 (except alopecia).
- Required initial laboratory values:
- Creatinine ≤ 2.0mg/dL
- total or direct bilirubin ≤ 1.5mg/dL; SGPT (ALT) ≤ 3xULN
- negative pregnancy test for women with child-bearing potential.
- Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
- Subjects must have a left ventricular ejection fraction (LVEF) of ≥ 45%.
Who cannot join
- Subjects with FAB M3 (t (15; 17) (q22; q21) [PML-RARα]) are not eligible.
- Subjects must not be receiving any chemotherapy agents (except Hydroxyurea).
- Intrathecal methotrexate and cytarabine are permissible.
- Subjects must not be receiving growth factors, except for erythropoietin.
- Subjects with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.
- Subjects 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.
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- Subjects taking the following are not eligible:
- Carbamazepine (e.g., Tegretol)
- Rifabutin (e.g., Mycobutin) or
- Rifampin (e.g., Rifadin)
- Rifapentine (e.g., Priftin)
- St. John's wort
- Clarithromycin (e.g., Biaxin)
- Cyclosporine (e.g. Neoral or Sandimmune)
- Diltiazem (e.g., Cardizem)
- Erythromycin (e.g., Akne-Mycin, Ery-Tab)
- Itraconazole (e.g., Sporanox)
- Ketoconazole (e.g., Nizoral)
- Telithromycin (e.g., Ketek)
- Verapamil (e.g., Calan SR, Isoptin, Verelan)
- Voriconazole (e.g., VFEND)
- Tacrolimus (e.g. Prograf) Subjects taking fluconozole, voriconizole, itraconazole, posaconazole, and ketokonazole within 72 hours of study drug starting are not eligible. Reinstitution of fluconozole, voriconizole, itraconazole, posaconazole, ketokonazole and diltiazem is permissible 72 hours after the last dose of sirolimus.
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Biomarker Validation Study to Establish Whether Serial Flow Cytometric Measurements Predict Clinical Response to Sirolimus and MEC (Mitoxantrone Etoposide Cytarabine) Treatment in Patients With High-Risk Acute Myelogenous Leukemia
This pilot phase II trial studies whether biomarkers (biological molecules) in bone marrow samples can predict treatment response to sirolimus and chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) in patients with acute myeloid leukemia (AML) that is likely to come back or spread (high-risk). Sirolimus inhibits or blocks the pathway that causes cancer cells to grow. Adding sirolimus to standard chemotherapy may help improve patient response. Studying samples of bone marrow from patients treated with sirolimus in the laboratory may help doctors learn whether sirolimus reverses or turns off that pathway and whether changes in biomarker levels can predict how well patients will respond to treatment.
Read the detailed description
PRIMARY OBJECTIVES:
- To test the association between biochemical response and clinical response.
SECONDARY OBJECTIVES:
- To estimate complete response rate of sirolimus MEC in patients with high risk AML.
II. To estimate progression free survival in this patient population. III. To collect further information on the safety, tolerability, and efficacy of sirolimus in combination with MEC in patients with relapsed or refractory myeloid malignancies.
OUTLINE:
Patients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus orally (PO) on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride intravenously (IV) over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8.
After completion of study treatment, patients are followed up every 3 months for 2 years.
- Conditions
- Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia
- Being tested
- Sirolimus, Mitoxantrone, Etoposide, Cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
Given PO
MitoxantroneDrug
Also called Mitoxantrone hydrochloride, Novantrone
Given IV
EtoposideDrug
Also called Etoposide phosphate, VP-16, Etopophos
Given IV
CytarabineDrug
Also called Cytosine arabinoside, Cytosar-U, Depocyt, ara-C
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus, MEC chemotherapy | Experimental | Patients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus PO on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride IV over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8. Receives: Drug: Sirolimus; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Response
Defined by change in phosphorylated ribosomal protein S6 (pS6) positive blasts, measured as the % reduction in pS6 positive blasts from baseline to day 4. Biochemical response will be described by mean, median, standard deviation, range and coefficient of variation. The association between biochemical response and clinical response will be tested by Fisher's exact test.
Measured: Baseline to day 4
Clinical Response
Clinical response was assessed at Day 45 using IWG criteria: Complete Remission (CR), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), Partial Remission (PR), or No Response (NR). CR requires normalized blood counts and bone marrow blasts <5%. CRp meets CR except platelet recovery; CRi meets CR except incomplete neutrophil/platelet recovery. PR is ≥50% reduction in marrow blasts to 5-25% with partial blood count improvement. NR indicates failure to meet these criteria. Tumor response per RECIST v1.0: CR = disappearance of all target lesions; PR = ≥30% decrease in sum of longest diameters; Overall Response = CR + PR. Progression = ≥20% increase in sum of longest diameters, measurable increase in non-target lesion, or new lesions.
Measured: Day 45
Secondary outcomes (3)
Overall Response Rate (ORR) (Complete Response [CR], CR With Incomplete Platelet Recovery [CRp], or Partial Response)
Fraction of patients who achieve CR, CRp, or PR will be assessed. ORR and 95% exact confidence interval will be computed for all patients and for sensitive and resistant subgroups.
Measured: Day 45
Relapse Free Survival (RFS)
RFS will be estimated by the Kaplan-Meier method. A landmark analysis of RFS by clinical response (CR+CRp, CRi, PR or no response [NR]) will be computed from day 45 marrow assessment. Median values and 95% confidence intervals will be calculated.
Measured: Time from study entry to first documented progression, death, or last contact, assessed up to 2 years
Percentage of Participants by Risk Group
Overall Survival (OS) is defined as the time from study entry to death or last contact. OS will be analyzed by risk groups: Favorable, Intermediate, and Poor/Adverse, based on baseline factors such as cytogenetics, molecular markers, and clinical characteristics. These risk groups are used to predict clinical outcomes, with favorable indicating longer survival expectancy, intermediate suggesting moderate outcomes, and poor/adverse indicating more aggressive disease with lower survival rates. Results will be reported as the percentage of participants in each risk category.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study start7 Oct 2015
- Primary completion17 Apr 2023
- Study completion17 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Adult Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margaret Kasner, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02583893
- Sponsor's protocol ID
- 15D.377
- Other IDs
- 2013-087, NCI-2015-01507, JT 5530
- Status last verified
- May 2026
- First submitted
- 8 Oct 2015
- Last updated
- 29 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Biomarker Validation Study to Establish Whether Serial Flow Cytometric Measurements Predict Clinical Response to Sirolimus and MEC (Mitoxantrone Etoposide Cytarabine) Treatment in Patients With High-Risk Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT02583893
- Acronym / sponsor ID
- 15D.377
- Conditions
- Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- 7 Oct 2015 (actual)
- Primary completion
- 17 Apr 2023 (actual)
- Study completion
- 17 May 2023 (actual)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot phase II trial studies whether biomarkers (biological molecules) in bone marrow samples can predict treatment response to sirolimus and chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) in patients with acute myeloid leukemia (AML) that is likely to come back or spread (high-risk). Sirolimus inhibits or blocks the pathway that causes cancer cells to grow. Adding sirolimus to standard chemotherapy may help improve patient response. Studying samples of bone marrow from patients treated with sirolimus in the laboratory may help doctors learn whether sirolimus reverses or turns off that pathway and whether changes in biomarker levels can predict how well patients will respond to treatment.
Detailed description
PRIMARY OBJECTIVES:
- To test the association between biochemical response and clinical response.
SECONDARY OBJECTIVES:
- To estimate complete response rate of sirolimus MEC in patients with high risk AML.
II. To estimate progression free survival in this patient population. III. To collect further information on the safety, tolerability, and efficacy of sirolimus in combination with MEC in patients with relapsed or refractory myeloid malignancies.
OUTLINE:
Patients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus orally (PO) on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride intravenously (IV) over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus, MEC chemotherapy | Experimental | Drug: Sirolimus, Drug: Mitoxantrone, Drug: Etoposide, Drug: CytarabinePatients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus PO on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride IV over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:
- Subjects must be ≥ 18 years of age.
- Subjects must have an ECOG performance status of 2 or less (see Appendix1).
- Subjects must have a life expectancy of at least 4 weeks.
- Subjects must be able to consume oral medication.
Key exclusion criteria (22 listed)
- Subjects with FAB M3 (t (15; 17) (q22; q21) [PML-RARα]) are not eligible.
- Subjects must not be receiving any chemotherapy agents (except Hydroxyurea).
- Subjects must not be receiving growth factors, except for erythropoietin.
- Subjects with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.
- Subjects 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamycinGiven PO | Drug | Sirolimus, MEC chemotherapy |
| MitoxantroneAlso: Mitoxantrone hydrochloride, NovantroneGiven IV | Drug | Sirolimus, MEC chemotherapy |
| EtoposideAlso: Etoposide phosphate, VP-16, EtopophosGiven IV | Drug | Sirolimus, MEC chemotherapy |
| CytarabineAlso: Cytosine arabinoside, Cytosar-U, Depocyt, ara-CGiven IV | Drug | Sirolimus, MEC chemotherapy |
Primary outcome
Biochemical Response
Time frame: Baseline to day 4
Defined by change in phosphorylated ribosomal protein S6 (pS6) positive blasts, measured as the % reduction in pS6 positive blasts from baseline to day 4. Biochemical response will be described by mean, median, standard deviation, range and coefficient of variation. The association between biochemical response and clinical response will be tested by Fisher's exact test.
Clinical Response
Time frame: Day 45
Clinical response was assessed at Day 45 using IWG criteria: Complete Remission (CR), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), Partial Remission (PR), or No Response (NR). CR requires normalized blood counts and bone marrow blasts <5%. CRp meets CR except platelet recovery; CRi meets CR except incomplete neutrophil/platelet recovery. PR is ≥50% reduction in marrow blasts to 5-25% with partial blood count improvement. NR indicates failure to meet these criteria. Tumor response per RECIST v1.0: CR = disappearance of all target lesions; PR = ≥30% decrease in sum of longest diameters; Overall Response = CR + PR. Progression = ≥20% increase in sum of longest diameters, measurable increase in non-target lesion, or new lesions.
3 secondary outcomes
Overall Response Rate (ORR) (Complete Response [CR], CR With Incomplete Platelet Recovery [CRp], or Partial Response)
Time frame: Day 45
Relapse Free Survival (RFS)
Time frame: Time from study entry to first documented progression, death, or last contact, assessed up to 2 years
Percentage of Participants by Risk Group
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Jefferson University HospitalsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret Kasner, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus, Mitoxantrone and Etoposide in people with Recurrent Adult Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biochemical Response (time frame: Baseline to day 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.