Sertraline and Cytosine Arabinoside in Adults With Relapsed and Refractory AML
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I study with the goals of determining the feasibility, safety, and toxicity
      of administering sertraline in combination with timed-sequential cytosine arabinoside (ara-C)
      in adults with relapsed and refractory acute myeloid leukemia (AML).

      Primary objective:

        -  To define the maximum tolerated dose (MTD) and Recommended Phase II Dose (RP2D) of
           sertraline administered in combination with timed-sequential cytosine arabinoside in
           adult patients with relapsed and refractory acute myeloid leukemia.

        -  To evaluate the safety and tolerability of sertraline given in combination with
           timed-sequential cytosine arabinoside in adult patients with relapsed and refractory
           acute myeloid leukemia.
    

Detailed description: 
      Relapsed and refractory acute myeloid leukemias are characterized by net drug resistance. At
      the root of this drug resistance is an enhanced survival that relates to intrinsic cell cycle
      dysregulation and aberrations in the overall process of the repair of DNA damage. These
      malignancies represent a continuing therapeutic challenge, since currently no "standard
      treatments" for these diseases exist. Approximately 30% of adults with newly diagnosed AML
      are primary refractory to chemotherapy and at least 50% of those who achieve remission will
      relapse. For patients with relapsed or refractory AML, the expected CR/CRi rates with
      traditional multi-agent chemotherapies range from < 10% for primary refractory AML to 25-30%
      for relapsed AML and cure rates < 20%, even with allogeneic stem cell transplantation. Thus,
      novel treatment approaches are needed.
    

Intervention name(s): Sertraline; Cytosine arabinoside; allogeneic stem cell transplantation
Intervention type(s): Drug; Drug; Procedure
Intervention description(s): Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is FDA approved to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.
Sertraline will be administered orally twice a day starting on day -3. Sertraline will be administered at one of 4 pre-defined dose levels in the following dose-escalation: 50 mg daily, 50 mg twice a day, 50 mg every morning (QAM) and 100 mg every evening (QPM), 100 mg twice a day. 100 mg QAM and 150 mg QPM.; Cytarabine is a cytotoxic chemotherapy approved for use in acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelogenous leukemia. It is also approved to prevent and treat meningeal leukemia. Cytarabine kills cells in S-phase through inhibition of DNA polymerase, as well as by halting DNA synthesis after its incorporation into DNA.
Cytosine arabinoside (Ara-C) will be administered as a 72 hour intravenous continuous infusion (IVCI) beginning Day 1 of therapy and again beginning Day 10 of therapy. The total dose of ara-C for each 72 hour period is 2 gm/m2 (0.667 gm/m2/24 hours).; Allogeneic stem cell transplantation involves transferring the stem cells from a healthy person (the donor) to a patient after high-intensity chemotherapy or radiation.
Other intervention name(s): Zoloft; ara-C; Cytarabine; allogeneic SCT
Intervention MeSH terms: Cytarabine; Sertraline
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Sertraline; Cytosine Arabinoside; Relapsed AML; Refractory AML