Low-Dose Daunorubicin in Relapsed/Refractory Acute Leukemia

NCT02914977 | Completed Phase 1 DMC

• 1 other identifier: IIT-2016-RP-HEM-LD-DNR
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lymphocytic Leukemia; Acute Myeloid Leukemia

Keywords

Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (3)

• Number of participants with treatment-related adverse events and/or toxicity as assessed by CTCAE 4.03.

  12 months

• Maximum Plasma Concentration [Cmax]

  prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing

• Area Under the Curve [AUC]

  prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing

Other Outcomes (1)

• 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.

  12 months

Study Arms (1)

Low-dose daunorubicin (DNR)

EXPERIMENTAL

Eligible patients will be treated with 5 days of low dose daunorubicin (DNR) for one cycle only.

Drug: Daunorubicin

Interventions

Daunorubicin DRUG

* Agent: Daunorubicin * Dose: 6.75 mg/m2/day * Route: IV * Schedule: Days 1-5 * Duration: One cycle

Also known as: Cerubidine, Daunoxome

Low-dose daunorubicin (DNR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• AML which has relapsed after Complete Remission
• AML which has been refractory to two prior induction attempts
• ALL which has relapsed after Complete Remission
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tara Lin: lead

Study Sites (1)

University of Kansas Cancer Center - Clinical Research Center

Fairway, Kansas, 66205, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Recurrence

Interventions

Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Tara Lin, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: September 26, 2016
• Study Start: November 1, 2016
• Primary Completion: April 3, 2019
• Study Completion: July 15, 2021
• Last Updated: January 14, 2022

Record last verified: 2022-01

Locations

US (1)