Details

Details

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)

IRB S1203

CC 13-415

Hospital Main Campus

Phase Phase 3

Disease Leukemia - Acute Myeloid (AML)

Drug Cytosine Arabinoside, Daunorubicin, Idarubicin, Vorinostat

Description

Description

Primary Objective
  1. (Chemotherapy): To compare event-free survival (EFS) between patients with AML who receive standard 7+3 or idarubicin and high-dose cytarabine {lA) to patients who receive lA + vorinostat.
  2. (Transplant): To determine whether it is possible to get 60% or more of adults with high-risk AMLin first complete remission (CR1) to allogeneic hematopoietic cell transplantation (HCT).
Secondary Objectives
  1. (Chemotherapy): To estimate the frequency and severity of toxicities of the three regimens in this patient population.
  2. (Transplant): To estimate disease-free survival (DFS) among patients who receive transplant.
  3. (Chemotherapy): To compare event-free survival (EFS) between patients who receive standard 7+3 to patients who receive lA.
  4. (Chemotheiapy/Tianslational v1edicine): To estimate the pievalence of the mutations NPM1, IDH1, IDH2, TET2 and DMT3A and the cytogenetic risk distribution of patients on this study and to evaluate the association between these and overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and complete remission rate.
  5. (Chemotherapy): To compare the complete response rate, disease-free survival (DFS), and overall survival (OS) between patients who receive standard 7+3 therapy or lA to patients who receive lA + vorinostat.
Additional Objectives
  1. (Chemotherapy/Translational Medicine): Future planned studies will include testing of histone H3 acetylation, induction of gammaH2AX, analysis of ROS resistance and DNA methylation profiles.
Inclusion Criteria

Inclusion Criteria

  1. 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 WHO diagnostic criteria for AML. Patients with acute promyelocytic leukemia (APL, FAB, M3) or blastic transformation of chronic myelogenous leukemia (CML) are not eligible. Patients with known CBF or FL T3 related leukemias are eligible for this study, but should preferentially be placed on NCI-sponsored protocols specific for these subtypes, if available.
  2. Patients must have diagnostic/pre-treatment specimens obtained within 28 days prior to registration submitted as outlined in Section 15.2 for cytogenetic (and 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)], 11 q23 rearrangement [except t(9;11 )], 17p-, t(6;9), t(9;22), complex (at least 3 unrelated 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 as outlined in Section 12.0.
  3. Patients must be chemo-naive, i.e., not have received any prior Induction chemotherapy for AML or 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/m2 daunorubicin or equivalent. Prior ATRA for suspected APL is allowed. Prior methotrexate for CNS involvement is allowed. Patients with prior history of MDS must not have received azacitidine, decitabine, lenalidomide or vorinostat.
  4. Patients must have peripheral blood and bone marrow aspirate specimens obtained within 28 days prior to registration submitted for translational medicine as outlined in Section 15.1. With patient consent, residuals will be banked for future research.
  5. Patients must be ≥ 18 and ≤ 60 years of age.
  6. Patients must have Zubrod Performance Status ≤ 3 (see Section 10.7).
  7. Patients must have either ECHO or MUGA with ejection fraction ≥ 45% within 28 days prior to registration.
  8. Patients must not have prolonged QTc interval (> 500 msec) determined by EKG within 28 days prior to registration.
  9. Patients must not have cardiac disease defined as: New York Heart Association (NYHA) > Class II (see Appendix 18.2). 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.
  10. 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.
  11. Patients who are known to be HIV+ are eligible providing they meet all of the following additional criteria within 28 days prior to registration:
    • CD4 cells ≥ 500/mm3
    • Viral load of ≤ 50 copies HIV mRNA/mm3 if on cART or ≤ 25,000 copies 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.

  12. Patients with known Hepatitis B or Hepatitis C infection may be eligible providing they have viral load ≤ 800,000 IU/L within 28 days prior to registration.
  13. Patients must be able to take oral medications.
  14. Patients must have a history and physical examination obtained within 28 days prior to registration.
  15. Patients must not be pregnant or nursing due to the teratogenic potential of the drugs used in this study. 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.
  16. Prior malignancy is allowed providing it does not require concurrent therapy. Exception: Active hormonal therapy is allowed.
  17. Patients must not be receiving valproic acid.
  18. 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
  19. As part of the OPEN registration process (see Section 13.4 for OPEN access instructions) 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.
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available