Acute Lymphocytic LeukemiaPhase 1NCT02914977
Low-Dose Daunorubicin in Relapsed/Refractory Acute Leukemia
A Phase 1 study testing Daunorubicin in people with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia, run by Tara Lin at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lymphocytic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- Daunorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 15 Jul 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Cancer Center - Clinical Research Center
Fairway, Kansas, 66205
About this study
Official title: 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.
Read the 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.
- Conditions
- Acute Lymphocytic Leukemia, Acute Myeloid Leukemia
- Being tested
- Daunorubicin
- Keywords
- Relapsed, Refractory
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaunorubicinDrug
Also called Cerubidine, Daunoxome
- Agent: Daunorubicin
- Dose: 6.75 mg/m2/day
- Route: IV
- Schedule: Days 1-5
- Duration: One cycle
| Study group | Role | What they receive |
|---|---|---|
| Low-dose daunorubicin (DNR) | Experimental | Eligible patients will be treated with 5 days of low dose daunorubicin (DNR) for one cycle only. Receives: Drug: Daunorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (3)
Number of participants with treatment-related adverse events and/or toxicity as assessed by CTCAE 4.03.
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).
Measured: 12 months
Maximum Plasma Concentration [Cmax]
Measured: prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing
Area Under the Curve [AUC]
Measured: prior to dosing and 5, 20, and 40 min and 1, 2, 4, 8, and 24 hrs after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2016 (estimated)
- Study startNov 2016
- Primary completion3 Apr 2019
- Study completion15 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tara Lin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tara Lin, University of Kansas Medical Center
- Investigators
- Tara Lin, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02914977
- Sponsor's protocol ID
- IIT-2016-RP-HEM-LD-DNR
- Status last verified
- Jan 2022
- First submitted
- 25 Jul 2016
- Last updated
- 14 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Low-Dose Daunorubicin in Patients With Relapsed/Refractory Acute Leukemia
- ClinicalTrials.gov ID
- NCT02914977
- Acronym / sponsor ID
- IIT-2016-RP-HEM-LD-DNR
- Conditions
- Acute Lymphocytic Leukemia, Acute Myeloid Leukemia
- Keywords
- Relapsed, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Tara LinUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- 3 Apr 2019 (actual)
- Study completion
- 15 Jul 2021 (actual)
- First posted
- 26 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Low-dose daunorubicin (DNR) | Experimental | Drug: DaunorubicinEligible patients will be treated with 5 days of low dose daunorubicin (DNR) for one cycle only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaunorubicinAlso: Cerubidine, Daunoxome* Agent: Daunorubicin * Dose: 6.75 mg/m2/day * Route: IV * Schedule: Days 1-5 * Duration: One cycle | Drug | Low-dose daunorubicin (DNR) |
Primary outcome
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
3 secondary outcomes
Number of participants with treatment-related adverse events and/or toxicity as assessed by CTCAE 4.03.
Time frame: 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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2022.
Related trials for Acute Lymphocytic Leukemia
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 1
In VIVO CAR-T Therapy for Relapsed/Refractory Hematological Malignancies
B-Acute Lymphoblastic Leukemia, B Cell Non-Hodgkin's Lymphoma
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tara Lin, MD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Daunorubicin in people with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia, run by Tara Lin at 1 site 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 13 inclusion and 8 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 14 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2022.