Biomarkers for Personalized Early Assessment of Response During Salvage Chemotherapy in People With Relapsed or Refractory Acute Myeloid Leukemia (PEARL15)
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Observational

Summary: 
      Background:

      -Acute myeloid leukemia (AML) is a cancer of the white blood cells. It can be fatal. Standard
      treatment involves intensive chemotherapy. Not all treatment works. AML that has not
      responded to treatment (refractory) or that has returned after treatment (relapsed) is
      high-risk even with treatment. Success of therapy is normally determined after 28 to 56 days.
      This study will see if a blood test on day 4 of therapy can help identify earlier those who
      will not respond.

      Objectives:

      -To see if a blood test on day 4 of therapy can help identify those who will not respond to
      treatment for AML.

      Eligibility:

      -People ages 18-70 who have refractory or relapsed AML and have had at least one previous
      therapy for it.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood tests.

        -  Participants will have:

        -  Several blood tests.

        -  Bone marrow exams: a needle is inserted into the hip to take cells from the bone marrow.

        -  Echocardiogram: a small probe is held to the chest to take pictures of the heart.

        -  ECG: soft electrodes are stuck to the skin. A machine records the heart s signals.

        -  CT scans: they will lie in a machine that takes pictures of the body.

        -  Standard chemotherapy.

        -  Possible transfusions of blood products such as red blood cells or platelets.

        -  Participants will be expected to stay in the study typically for 2 3 months. This will
           include inpatient treatment. Inpatient stay normally will be 1 or 2 months.
    

Detailed description: 
      Effective treatment of patients with relapsed and refractory acute myeloid leukemia (RR-AML)
      remains a significant unmet need. Current response criteria were originally proposed in 1956
      and do not provide a sensitive assessment of AML disease burden, as evidenced by the
      disconnect between the apparent success of current induction therapy in achieving complete
      remission in most patients and the stark reality of median overall survival times of less
      than two years. While sensitive minimal/measurable residual disease assays assessing AML
      disease burden have been developed, the role for these tests in the treatment algorithm for
      patients with RR-AML has yet to be defined. We propose evaluating if these high sensitivity
      assays could function as early predictors of salvage therapy failure.

      This protocol is designed as a feasibility study to evaluate if use of high sensitivity
      peripheral blood-based molecular assays on day 4 of induction salvage chemotherapy can
      predict failure to ultimately achieve a CR or CRi in patients with RR-AML. Eligible patients
      will receive salvage induction therapy using FDA approved antineoplastic agents given either
      alone or in combinations as defined in the National Comprehensive Cancer Network (NCCN)
      Clinical Practice Guidelines in Oncology for AML.

      Additional secondary objectives include investigating the relationship between kinetics of
      gene expression changes and response to chemotherapy, determining the proportion of patients
      for whom results of day 4 peripheral blood gene expression testing are available before day 8
      of therapy, determining the proportion of patients for whom results from pre-treatment
      molecular and genetic testing are available before day 8 of therapy, assessing patient and
      disease specific factors associated with failure to achieve a CR, determining the feasibility
      of measuring AML residual disease burden using alternative technologies and alternative
      tissue sources, determining the proportion of patients who receive allogeneic hematopoietic
      stem cell transplant after completion of therapy, determining the incidence of infectious
      complications with the use of modern prophylactic antimicrobial agents compared with
      historical comparisons and determining the feasibility of recruiting patients with RR-AML to
      the NIH Clinical Center.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Measurable Residual Disease; Relapsed/Refractory AML; Salvage Chemotherapy