Adult Acute Megakaryoblastic Leukemia (M7)Early Phase 1NCT01822015

Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

A Early Phase 1 study testing Sirolimus, Idarubicin and Cytarabine in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
What is being tested?: Sirolimus, Idarubicin and Cytarabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 55 participants
Where: 1 siteUnited States
Study dates: 15 Mar 2013to 12 Dec 2019
Phase: Early Phase 1

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 newly diagnosed acute myeloid leukemia (non-M3 AML) as documented by the presence of >20% myeloid blasts in the bone marrow
Subjects must be 18 years of age and <= 60
Subjects must have an ECOG performance status of 2 or less. (see attachment 1).
Subjects must have a life expectancy of at least 4 weeks.
Subjects must be able to consume oral medication.
Required initial laboratory values: Creatinine 2.0mg/dL; total or direct bilirubin 1.5mg/dL; SGPT(ALT) 3xULN (if not due to the leukemia itself); 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 APL - FAB M3 (t(15;17)(q22;q21)[PML-RAR] are not eligible
Subjects must not have received any chemotherapeutic agents for the AML (except Hydroxyurea). Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
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.
Subjects taking the following are not eligible:

Show all 27Show fewer

Carbamazepine (e.g., Tegretol)
Rifabutin (e.g., Mycobutin)
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 fluconazole, voriconazole, itraconazole, posaconazole, and ketoconazole within 72 hours of study entry are not eligible. Reinstitution of fluconazole, voriconazole, itraconazole, posaconazole, ketoconazole and diltiazem is permissible 72 hours after the last dose of sirolimus.
Subjects who require HIV protease inhibitors or those with AIDS-related illness
Subjects with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.
Subjects 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 sirolimus. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
Subjects 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.
Subjects with bacteremia must have documented negative blood cultures prior to study entry.

Trial locations and contacts

1 site in 1 country.

United States1 site

Thomas Jefferson University
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia

This pilot clinical trial studies sirolimus, idarubicin, and cytarabine in treating patients with newly diagnosed 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 idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sirolimus together with idarubicin and cytarabine may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

To determine whether there is an association between baseline mammalian target of rapamycin (mTOR) activation paired with mTOR target inhibition post-treatment in leukemic blasts and clinical response in patients with newly diagnosed acute myeloid leukemia (AML) treated with sirolimus idarubicin/cytarabine.

SECONDARY OBJECTIVES:

To estimate the response rate of sirolimus idarubicin/cytarabine in patients with newly diagnosed AML compared to historical data using idarubicin/cytarabine alone.
To determine the ability of oral sirolimus to inhibit mTOR in leukemic blasts.
To assess if mTOR pathway inhibition correlates with clinical response.
To collect further information on the safety, tolerability, and efficacy of sirolimus in combination with idarubicin/cytarabine in patients with newly diagnosed AML.
To describe the progression-free survival and overall survival (1 year, 2 year and 5 year) of patients treated with sirolimus idarubicin/cytarabine.

OUTLINE:

Patients receive sirolimus orally (PO) once daily (QD) on days 1-10, idarubicin intravenously (IV) over 3-5 minutes on days 4-6, and cytarabine IV continuously over 24 hours on days 4-10.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Conditions: Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Being tested: Sirolimus, Idarubicin, Cytarabine
Medical subject headings: Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SirolimusDrug
Also called rapamycin, Rapamune
Given PO
IdarubicinDrug
Also called 4-demethoxydaunorubicin, Zavedos, Idamycin
Given IV
CytarabineDrug
Also called cytosine arabinoside, Cytosar-U, Depocyt, Ara-C
Given IV

Study groups in NCT01822015
Study group	Role	What they receive
Treatment (sirolimus, idarubicin, cytarabine)	Experimental	Patients receive sirolimus PO QD on days 1-10, idarubicin IV over 3-5 minutes on days 4-6, and cytarabine IV continuously over 24 hours on days 4-10. Receives: Drug: Sirolimus; Drug: Idarubicin; Drug: Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in measurement of mTOR activation paired with mTOR target inhibition
The association between mTOR response and clinical response (complete or partial response) will be evaluated using the two-sided Fisher's exact test with alpha 0.05.
Measured: Baseline to day 4

Secondary outcomes (4)

Overall survival
Will be evaluated using the Kaplan-Meier method stratified by mTOR response. Log rank test will be used to compare the overall survival in patients with and without mTOR response. Based on the estimated survival curves, the 1-year, 2-year, and 5-year survival rates will be computed with the corresponding 95% confidence intervals.
Measured: 1 year, 2 years, 5 years
Progression free survival
Based on the estimated survival curves, the 1-year, 2-year, and 5-year survival rates will be computed with the corresponding 95% confidence intervals.
Measured: 1 year, 2 years, 5 years
Incidence of toxicities, graded according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 4.0 guidelines
Safety data analysis is descriptive. All estimates of adverse events rates will be presented with corresponding confidence intervals using the exact method.
Measured: Up to 45 days
Response defined as patients achieving a complete remission (CR), complete response in absence of total platelet recovery (CRp), or partial remission (PR)
Proportions of complete response and partial response with be computed separately in patients with and without mTOR response and presented with corresponding exact binomial 95% confidence intervals.
Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 201312 Dec 2019

First posted1 Apr 2013 (estimated)
Study start15 Mar 2013
Primary completion12 Dec 2019
Study completion12 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (79)Papers the sponsor has linked to this study.
Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies 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: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01822015
Sponsor's protocol ID: 12D.588
Other IDs: 2012-55, JT 3038
Status last verified: Apr 2025
First submitted: 25 Mar 2013
Last updated: 29 Apr 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7.
PubMed 8634416
Gilliland DG, Jordan CT, Felix CA. The molecular basis of leukemia. Hematology Am Soc Hematol Educ Program. 2004:80-97. doi: 10.1182/asheducation-2004.1.80.
PubMed 15561678
Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Miclea JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. doi: 10.1182/blood-2003-10-3561. Epub 2004 May 13.
PubMed 15142880
Stone RM. The difficult problem of acute myeloid leukemia in the older adult. CA Cancer J Clin. 2002 Nov-Dec;52(6):363-71. doi: 10.3322/canjclin.52.6.363.
PubMed 12469764
Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. doi: 10.1200/JCO.2009.22.9088. Epub 2009 Dec 28.
PubMed 20038732
Buchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Muller-Tidow C, Braess J, Spiekermann K, Kienast J, Staib P, Gruneisen A, Kern W, Reichle A, Maschmeyer G, Aul C, Lengfelder E, Sauerland MC, Heinecke A, Wormann B, Hiddemann W. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol. 2009 Jan 1;27(1):61-9. doi: 10.1200/JCO.2007.15.4245. Epub 2008 Dec 1.
PubMed 19047294
Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. doi: 10.1056/NEJM199812033392301.
PubMed 9834301
Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol. 2007 May 10;25(14):1908-15. doi: 10.1200/JCO.2006.10.2731.
PubMed 17488990
Mayer RJ, Davis RB, Schiffer CA, Berg DT, Sarno E, Frei E 3rd. Intensive post-remission therapy with Ara-C in adults with acute myeloid leukemia: initial results of a CALGB phase III trial. The Cancer and Leukemia Group B. Leukemia. 1992;6 Suppl 2:66-7. No abstract available.
PubMed 1578945
Menzin J, Lang K, Earle CC, Kerney D, Mallick R. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med. 2002 Jul 22;162(14):1597-603. doi: 10.1001/archinte.162.14.1597.
PubMed 12123403
Bennett JM, Andersen JW, Cassileth PA. Long term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group (ECOG) experience. Leuk Res. 1991;15(4):223-7. doi: 10.1016/0145-2126(91)90124-c.
PubMed 2030603
Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51.
PubMed 8874180
Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, Okumura H, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2358-65. doi: 10.1182/blood-2010-03-273243. Epub 2010 Aug 6.
PubMed 20693429
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5;344(14):1031-7. doi: 10.1056/NEJM200104053441401.
PubMed 11287972
Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. doi: 10.1182/blood-2003-08-2958. Epub 2003 Oct 9.
PubMed 14551133