Sertraline and Cytosine Arabinoside in Adults With Relapsed and Refractory AML

• Status: Recruiting
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University; Mark G. Frattini
• Collaborator: The Leukemia and Lymphoma Society
• Treatments: Cytarabine; Sertraline

Criteria

Inclusion Criteria:

• Pathologically-confirmed diagnoses of relapsed AML: Patients with AML that have relapsed at least once or are primary induction failure will be eligible

• Age ≥ 18 and ≤ 70 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2

• ≥ 2 weeks off cytotoxic chemotherapy

• ≥ 2 weeks off radiation therapy

• Off biologic therapies including hematopoietic growth factors ≥ 1 week

• If using tyrosine kinase inhibitors (TKIs)/src inhibitors, other non-cytotoxics, or leukopheresis for blast count control, the patient must be off these therapies for > 24 hrs before starting sertraline. Hydroxyurea will be allowed with sertraline but should be stopped ≥24 hours before starting cytarabine.

• Adequate organ function as defined below:

• Renal function: Serum creatinine <2.0 mg/dL or creatinine clearance ≥ 50 mL/minute

• Hepatic function: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline Phosphatase ≤ 5x Upper Limit normal (ULN), bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's, hemolysis or leukemic infiltration

• Left Ventricular Ejection Fraction ≥ 45% by multigated acquisition (MUGA) scan or Echocardiogram

• Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are ≥ 8 weeks from stem cell infusion, have no active graft versus host disease (GVHD), are off immune suppression for at least 2 weeks, and do not have a history of veno-occlusive disease (VOD)

• Female patients of childbearing age must have negative pregnancy test and women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after study participation

• Patients must be able to give informed consent

Exclusion Criteria:

• Concomitant chemotherapy, radiation therapy, or immunotherapy

• Patients who are receiving any other investigational agents concurrently

• Hyperleukocytosis with ≥ 30,000 blasts/microliter (uL). If using tyrosine kinase/src inhibitors (FLT-3 inhibitors), other non-cytotoxics, or leukopheresis for blast count control, the patient must be off these therapies for ≥ 24 hours prior to beginning sertraline. If using hydroxyurea for blast count control, this may be continued until up to 24 hours before starting cytarabine

• Acute Progranulocytic Leukemia (APL)

• Active central nervous system (CNS) leukemia

• Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible

• Presence of other life-threatening illness

• Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol

• Pregnant women are excluded from this study due to potential teratogenic and/or abortifacient effect of this combination chemotherapy. Nursing mother should stop breastfeeding to be eligible due to potential risk for adverse events in nursing infant

• Subjects with the following cardiac risk factors must be excluded: transmural myocardial infarction (MI) within prior 6 months, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack (TIA) or seizure disorder within 6 months prior to study drug administration. In addition, patients with New York Heart Association (NYHA) class III or IV heart failure will be excluded

• Patients requiring treatment with other anti-depressive medications including the selective and non-selective monoamine oxidase (MAO) inhibitors (including linezolid), 5-hydroxytryptamine (5-HT) receptor agonists (triptans), tryptophan or antidopaminergic agents (anti-psychotics, metoclopramide, promethazine, haloperidol)

• Patients requiring prolonged treatment with fluconazole, voriconazole, or posaconazole. Use of isavuconazonium sulfate, liposomal amphotericin, are echinocandins are permitted

• Prior treatment with clofarabine within 6 months or history of clofarabine-induced liver dysfunction

• History of hypersensitivity to sertraline

• Patients taking sertraline at the time of study entry will not be eligible for the study