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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

18

Phase

  • 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

Ages Eligible for Study

16 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
Intervention / Treatment
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

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

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

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

Tara Lin

Investigators

  • 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)

November 1, 2016

Primary Completion (Actual)

April 3, 2019

Study Completion (Actual)

July 15, 2021

Study Registration Dates

First Submitted

July 25, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimate)

September 26, 2016

Study Record Updates

Last Update Posted (Actual)

January 14, 2022

Last Update Submitted That Met QC Criteria

January 12, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on Daunorubicin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe