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

Related Clinical Trial
Clinical Study of Anti-ILT3 CAR-T Therapy for R/R AML(M4/M5) CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia AML Therapy With Irradiated Allogeneic Cells Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission Genetic and Molecular Characteristics of Mexican Adults With Acute Myeloid Leukemia: a Prospective Multicentric Study. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)

Brief Title

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

Official Title

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

Brief Summary

      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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      1) 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:

        1. To estimate the response rate of sirolimus idarubicin/cytarabine in patients with newly
           diagnosed AML compared to historical data using idarubicin/cytarabine alone.

        2. To determine the ability of oral sirolimus to inhibit mTOR in leukemic blasts.

        3. To assess if mTOR pathway inhibition correlates with clinical response.

        4. To collect further information on the safety, tolerability, and efficacy of sirolimus in
           combination with idarubicin/cytarabine in patients with newly diagnosed AML.

        5. 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.
    

Study Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Change in measurement of mTOR activation paired with mTOR target inhibition

Secondary Outcome

 Overall survival

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

Sirolimus

Study Arms / Comparison Groups

 Treatment (sirolimus, idarubicin, cytarabine)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

55

Start Date

March 15, 2013

Completion Date

December 12, 2019

Primary Completion Date

December 12, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. 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

          2. Subjects must be 18 years of age and <= 60

          3. Subjects must have an ECOG performance status of 2 or less. (see attachment 1).

          4. Subjects must have a life expectancy of at least 4 weeks.

          5. Subjects must be able to consume oral medication.

          6. 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.

          7. Patients must be able to sign consent and be willing and able to comply with scheduled
             visits, treatment plan and laboratory testing.

          8. Subjects must have a left ventricular ejection fraction (LVEF) of >/= 45%.

        Exclusion Criteria:

          1. Subjects with APL - FAB M3 (t(15;17)(q22;q21)[PML-RAR] are not eligible

          2. 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).

          3. Subjects must not be receiving growth factors, except for erythropoietin.

          4. Subjects with a "currently active" second malignancy, other than non-melanoma skin
             cancers are not eligible.

          5. 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.

          6. Subjects taking the following are not eligible:

               1. Carbamazepine (e.g., Tegretol)

               2. Rifabutin (e.g., Mycobutin)

               3. Rifampin (e.g., Rifadin)

               4. Rifapentine (e.g., Priftin)

               5. St. John's wort

               6. Clarithromycin (e.g., Biaxin)

               7. Cyclosporine (e.g. Neoral or Sandimmune)

               8. Diltiazem (e.g., Cardizem)

               9. Erythromycin (e.g., Akne-Mycin, Ery-Tab)

              10. Itraconazole (e.g., Sporanox)

              11. Ketoconazole (e.g., Nizoral)

              12. Telithromycin (e.g., Ketek)

              13. Verapamil (e.g., Calan SR, Isoptin, Verelan)

              14. Voriconazole (e.g., VFEND)

              15. Tacrolimus (e.g. Prograf)

          7. 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.

          8. Subjects who require HIV protease inhibitors or those with AIDS-related illness

          9. 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.

         10. 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.

         11. 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.

         12. Subjects with bacteremia must have documented negative blood cultures prior to study
             entry.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Margaret Kasner, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01822015

Organization ID

12D.588

Secondary IDs

2012-55

Responsible Party

Sponsor

Study Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University


Study Sponsor

Margaret Kasner, MD, Principal Investigator, Thomas Jefferson University


Verification Date

February 2023