Cytarabine and Daunorubicin Hydrochloride or Idarubicin and Cytarabine With or Without Vorinostat in Treating Younger Patients With Previously Untreated Acute Myeloid Leukemia

Not Recruiting

Trial ID: NCT01802333


This randomized phase III trial studies cytarabine and daunorubicin hydrochloride or idarubicin and cytarabine with or without vorinostat to see how well they work in treating younger patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, idarubicin, and vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells. It is not yet known which combination chemotherapy is more effective in treating acute myeloid leukemia.

Official Title

A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy or Idarubicin With High Dose Cytarabine (IA) Versus IA With Vorinostat (NSC-701852) (IA + V) in Younger Patients With Previously Untreated Acute Myeloid Leukemia (AML)


Inclusion Criteria:


   - Patients must have morphologically confirmed newly diagnosed acute myelogenous
   leukemia (AML) with blood or bone marrow disease; patients with only extramedullary
   disease in the absence of bone marrow or blood involvement are not eligible; note:
   this protocol uses World Health Organization (WHO) diagnostic criteria for AML;
   patients with acute promyelocytic leukemia (APL, French-American-British [FAB], M3) or
   blastic transformation of chronic myelogenous leukemia (CML) are not eligible;
   patients with known core binding factor (CBF) or fms-like tyrosine kinase 3 (FLT3)
   related leukemias are eligible for this study, but should preferentially be placed on
   National Cancer Institute (NCI)-sponsored protocols specific for these subtypes, if

   - Patients must have diagnostic/pre-treatment specimens obtained within 28 days prior to
   registration submitted for cytogenetic (and fluorescent in situ hybridization [FISH]
   if possible) analysis to determine risk status; high risk classification will be
   defined as del(5q)/-5, del(7q)/-7, abn3q26 [inv(3)/t(3;3)], 11q23 rearrangement
   [except t(9;11)], 17p-, t(6;9), t(9;22), complex (at least 3 unrelated abnormalities
   [abn]), and monosomal karyotype (either loss of two different chromosomes or loss of
   one chromosome along with a structural chromosome abnormality other than add, ring and
   mar); karyograms and cytogenetics/FISH analysis reports must be submitted for
   discipline review

   - Patients must be chemo-naïve, i.e., not have received any prior induction chemotherapy
   for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis
   or hydroxyurea are allowed; prior anthracycline therapy is allowed, but must not
   exceed a dose of 200 mg/m^2 daunorubicin or equivalent; prior all-trans retinoic acid
   (ATRA) for suspected APL is allowed; prior methotrexate for central nervous system
   (CNS) involvement is allowed; patients with prior history of MDS must not have
   received azacitidine, decitabine, lenalidomide or vorinostat

   - Patients must have peripheral blood and bone marrow aspirate specimens obtained within
   28 days prior to registration submitted for translational medicine; with patient
   consent, residuals will be banked for future research

   - Patients must have Zubrod performance status =< 3

   - Patients must have either echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
   with ejection fraction >= 45% within 28 days prior to registration

   - Patients must not have prolonged corrected QT (QTc) interval (> 500 msec) determined
   by electrocardiogram (EKG) within 28 days prior to registration

   - Patients must not have cardiac disease defined as: New York Heart Association (NYHA) >
   class II; patients must not have unstable angina (angina symptoms at rest) or new
   onset angina (began within the last 3 months) or myocardial infarction within the past
   6 months

   - Patients must not have any coexisting medical condition that is likely to interfere
   with study procedures or results, and must be reasonable candidates for intensive
   chemotherapy, in the opinion of their treating physicians

   - Patients who are known to be human immunodeficiency virus (HIV) positive (+) are
   eligible providing they meet all of the following additional criteria within 28 days
   prior to registration:

      - Cluster of differentiation (CD) 4 cells >= 500/mm^3

      - Viral load < 50 copies of HIV messenger ribonucleic acid (mRNA)/mm^3 if on
      combination antiretroviral therapy (cART) or < 25,000 copies of HIV mRNA if not
      on cART

      - No zidovudine or stavudine as part of cART; patients who are HIV+ and do not meet
      all of these criteria are not eligible for this study

   - Patients with known hepatitis B or hepatitis C infection may be eligible providing
   they have viral load < 800,000 IU/mL within 28 days prior to registration

   - Patients must be able to take oral medications

   - Patients must have a history and physical examination obtained within 28 days prior to

   - Patients must not be pregnant or nursing; women/men of reproductive potential must
   have agreed to use an effective contraceptive method; a woman is considered to be of
   "reproductive potential" if she has had menses at any time in the preceding 12
   consecutive months; in addition to routine contraceptive methods, "effective
   contraception" also includes heterosexual celibacy and surgery intended to prevent
   pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
   bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
   previously celibate patient chooses to become heterosexually active during the time
   period for use of contraceptive measures outlined in the protocol, he/she is
   responsible for beginning contraceptive measures

   - Prior malignancy is allowed providing it does not require concurrent therapy;
   exception: active hormonal therapy is allowed

   - Patients must not be receiving valproic acid

   - All patients must be informed of the investigational nature of this study; patients or
   a legally authorized representative must sign and give written informed consent in
   accordance with institutional and federal guidelines

   - As part of the Oncology Patient Enrollment Network (OPEN) registration process the
   treating institution's identity is provided in order to ensure that the current
   (within 365 days) date of institutional review board approval for this study has been
   entered in the system


   - Patients may be registered for consolidation provided that they were eligible for the
   initial induction/re-induction registration and satisfy the following additional

      - Patients must have achieved morphologic remission (complete remission [CR] or
      complete remission with incomplete blood count recover [CRi]) after completion of
      induction or re-induction therapy; patient must remain in remission until
      beginning consolidation and this must be documented by bone marrow and peripheral
      blood examination within 28 days prior to registration to Step 2

      - All non-hematologic treatment related toxicities that are deemed clinically
      significant by the treating physician must have resolved to =< grade 2

      - Patients must not have received allogeneic stem cell transplant


drug: cytarabine

drug: daunorubicin hydrochloride

drug: vorinostat

other: laboratory biomarker analysis

drug: Idarubicin

procedure: allogeneic hematopoietic stem cell transplantation

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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