Low-Dose Daunorubicin in Relapsed/Refractory Acute Leukemia

January 12, 2022 updated by: Tara Lin

A Pilot Study of Low-Dose Daunorubicin in Patients With Relapsed/Refractory Acute Leukemia

In this pilot study, eligible patients will be treated with 5 days of low dose daunorubicin for one cycle only. Any patient who receives treatment on this protocol will be evaluable for toxicity. Each patient will be assessed for the development of toxicity at all scheduled visits (Days 1-5). Following participation on this brief pharmacodynamic trial, patients can then proceed to other conventional or investigational therapies, as clinically indicated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Disease relapse remains the primary challenge in the treatment of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). There is no standard of care treatment option for relapsed acute leukemia, and investigational therapies are recommended. Clinically targeting the leukemia stem cell (LSC) remains an unmet need in both AML and ALL. Therefore, a primary objective of this trial is to determine the molecular pharmacodynamic effects of low dose daunorubicin (DNR) on beta-catenin phosphorylation in serial bone marrow samples of patients with relapsed leukemia.

Prior to studying low-dose DNR in complex, multi-agent regimens, it is essential to confirm that it inhibits p-beta-catenin S552 in humans. This pilot study is designed to assess the feasibility and tolerability of low dose DNR administration to patients with relapsed/refractory AML and ALL, and obtain preliminary data regarding target engagement. A second objective is to demonstrate the safety and feasibility of low-dose daunorubicin administration in patients with relapsed/refractory acute leukemia.

Beta-catenin phosphorylation will be measured by immunohistochemistry assay in bone marrow samples taken from patients at study entry and at Day 8 following study therapy with low-dose DNR. The investigators will also measure the pharmacokinetics of low dose DNR in these patients, to enable preliminary PK-PD analyses and because there are essentially no PK data for DNR at comparable doses using modern analytical methodologies.

Following participation on this brief pharmacodynamic proof-of-concept trial, patients can then proceed to other conventional or investigational therapies, as clinically indicated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Fairway, Kansas, United States, 66205
        • University of Kansas Cancer Center - Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability to understand and the willingness to sign a written informed consent or have parental consent.
  • Age ≥ 18 years

  • Pathological confirmation by bone marrow documenting the following:

    1. AML which has relapsed after Complete Remission
    2. AML which has been refractory to two prior induction attempts
    3. ALL which has relapsed after Complete Remission
    4. ALL which has been refractory to two prior induction attempts
  • Disease status allows delay of additional anti-leukemia therapy for the duration of the study (hydroxyurea is allowed for control of WBC throughout study)
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3
  • Able to adhere to the study visit schedule and other protocol requirements
  • Cardiac ejection fraction ≥45% by ECHO
  • Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

Exclusion Criteria:

  • Concurrent use of conventional or investigational anticancer agents, except hydroxyurea (Standard prophylactic anti-infectives and medications to prevent/treat tumor lysis syndrome are allowed. Hydroxyurea may be used to keep the WBC<25,000. Additional anti-leukemia therapy is prohibited during the study.).
  • Patient has received chemotherapy or radiotherapy within 2 weeks prior to entering the study or has not recovered from adverse events due to agents administered more than 2 weeks earlier, with the exception of hydroxyurea.
  • Patients with known active uncontrolled central nervous system (CNS) leukemia
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to daunorubicin
  • Patients with a total lifetime anthracycline exposure exceeding the equivalent of 900 mg/m2 of daunorubicin
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Unwilling or unable to undergo serial bone marrow aspirate/biopsy
  • Pregnant or nursing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Low-dose daunorubicin (DNR)
Eligible patients will be treated with 5 days of low dose daunorubicin (DNR) for one cycle only.
Drug: Daunorubicin
  • Agent: Daunorubicin
  • Dose: 6.75 mg/m2/day
  • Route: IV
  • Schedule: Days 1-5
  • Duration: One cycle
Other Names:
  • Cerubidine
  • Daunoxome

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Molecular pharmacodynamic effect of low dose daunorubicin on beta-catenin phosphorylation as assessed by quantitative immunohistochemistry assay performed on serial bone marrow samples of patients with relapsed leukemia.
Time Frame: 12 months
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events and/or toxicity as assessed by CTCAE 4.03.
Time Frame: 12 months
Analyses will be performed for all patients having received at least one dose of study drug. Each patient will be assessed for the development of toxicity at all scheduled visits (Days 1-5).
12 months
Maximum Plasma Concentration [Cmax]
Time Frame: prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing
prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing
Area Under the Curve [AUC]
Time Frame: prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing
prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Test for additional validated markers for leukemia and/or stem cells (such as anti-CD34 and CD38, CD45 and/or CD19) assessed by flow cytometry of serial bone marrow samples.
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tara Lin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tara Lin, MD, University of Kansas Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 15, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 25, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 14, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IIT-2016-RP-HEM-LD-DNR

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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