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Acute Myeloid LeukemiaPhase 1NCT02891278

Sertraline and Cytosine Arabinoside in Adults With Relapsed and Refractory AML

A Phase 1 study testing Sertraline, Cytosine arabinoside and allogeneic stem cell transplantation in people with Acute Myeloid Leukemia, run by Columbia University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Sertraline, Cytosine arabinoside and allogeneic stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
2 sitesUnited States
Study dates
11 Aug 2016to 17 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University Medical Center

    Baltimore, Maryland, 21287

  • Columbia University

    New York, New York, 10032

Other trials in United States

About this study

Official title: 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.
Read the 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.

Being tested
Sertraline, Cytosine arabinoside, allogeneic stem cell transplantation
Keywords
Leukemia, Sertraline, Cytosine Arabinoside, Relapsed AML, Refractory AML
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SertralineDrug

    Also called Zoloft

    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.

  • Cytosine arabinosideDrug

    Also called ara-C, Cytarabine

    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 transplantationProcedure or surgery

    Also called allogeneic SCT

    Allogeneic stem cell transplantation involves transferring the stem cells from a healthy person (the donor) to a patient after high-intensity chemotherapy or radiation.

Study groups in NCT02891278
Study groupRoleWhat they receive
Sertraline with cytosine arabinosideExperimentalAll subjects will receive the following: Induction phase * Sertraline, twice daily at one of the pre-defined dose levels * Cytosine arabinoside, on days 1 and 10 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: * Allogeneic SCT and off study * Repeat cycle of oral sertraline and cytosine arabinoside IV infusion * Maintenance phase with sertraline for cycles of 28 days in length
Receives: Drug: Sertraline; Drug: Cytosine arabinoside; Procedure: allogeneic stem cell transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of sertraline administered in combination with timed-sequential cytosine arabinoside

    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.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2016 (estimated)
  2. Study start11 Aug 2016
  3. Primary completion17 Nov 2020
  4. Study completion17 Nov 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02891278
Sponsor's protocol ID
AAAQ8444
Other IDs
6474-15
Status last verified
Apr 2023
First submitted
1 Sep 2016
Last updated
12 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sertraline, Cytosine arabinoside and allogeneic stem cell transplantation in people with Acute Myeloid Leukemia, run by Columbia University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of sertraline administered in combination with timed-sequential cytosine arabinoside (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02891278.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2023.

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