- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02891278
Sertraline and Cytosine Arabinoside in Adults With Relapsed and Refractory AML
The Clinical Application of Tumor Reversion: A Phase I Study of Sertraline (Zoloft) in Combination With Timed-sequential Cytosine Arabinoside (Ara-C) in Adults With Relapsed and Refractory Acute Myeloid Leukemia (AML)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University Medical Center
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New York
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New York, New York, United States, 10032
- Columbia University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sertraline with cytosine arabinoside
All subjects will receive the following: Induction phase
Consolidation phase Patients who achieve complete remission (CR) or complete remission with incomplete count recovery (CRi) and are eligible for allogeneic stem cell transplantation will receive one of the following:
|
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.
Other Names:
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).
Other Names:
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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of sertraline administered in combination with timed-sequential cytosine arabinoside
Time Frame: Up to 24 months
|
Standard 3+3 dose-escalation design will be used to determine the MTD.
The MTD will be determined as the highest dose level where 1/6 patients experience dose-limiting toxicity (DLT).
Three patients will be treated at a given dose level combination and observed for at least 4 weeks to assess toxicity.
Doses will not be escalated in any individual patient.
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Up to 24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Daniel Lee, MD, Columbia University
- Principal Investigator: Joseph Jurcic, MD, Columbia University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Sertraline
- Cytarabine
Other Study ID Numbers
- AAAQ8444
- 6474-15 (Other Grant/Funding Number: Leukemia and Lymphoma Society)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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