Low-Dose Daunorubicin in Relapsed/Refractory Acute Leukemia
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|ClinicalTrials.gov Identifier: NCT02914977|
Recruitment Status : Active, not recruiting
First Posted : September 26, 2016
Last Update Posted : June 24, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphocytic Leukemia Acute Myeloid Leukemia||Drug: Daunorubicin||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Low-Dose Daunorubicin in Patients With Relapsed/Refractory Acute Leukemia|
|Actual Study Start Date :||November 2016|
|Actual Primary Completion Date :||April 3, 2019|
|Estimated Study Completion Date :||November 2020|
Experimental: Low-dose daunorubicin (DNR)
Eligible patients will be treated with 5 days of low dose daunorubicin (DNR) for one cycle only.
- 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 ]
- 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).
- 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 ]
- 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 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02914977
|United States, Kansas|
|University of Kansas Cancer Center - Clinical Research Center|
|Fairway, Kansas, United States, 66205|
|Principal Investigator:||Tara Lin, MD||University of Kansas Medical Center|