Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML

November 28, 2022 updated by: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

A Dose-escalated Phase Ⅰ Trial to Assess the Tolerance and Pharmacokinetics of Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML Patient

This phase Ⅰ study of Donafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, is to assess safety and pharmacokinetics in patients with Relapsed AML.

Study Overview

Status

Status

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

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

Donafenib is a multikinase inhibitor which is acting on various cellular pathways involved in the genesis of acute myeloid leukemia (AML). Donafenib is therefore a promising candidate for improvement of chemotherapy results in AML. This clinical trial evaluates the safety and pharmacokinetics of Donafenib combination with Cytarabine/Daunorubicin for AML in patients between 18 and 55 years of age.

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.
8

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

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Institute of Hematology and Blood Disease Hospital

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 to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with diagnosed AML (except APL) according to the FAB and WHO classification, including AML evolving from MDS or other hematologic diseases and AML after previous cytotoxic therapy or radiation (secondary AML) .
  • Patients with diagnosed Relapsed AML according to Chinese Guidelines for the Diagnosis and Treatment of Acute Myeloid Leukemia.
  • relapse after 6 months of an morphological remission.
  • Age ≥ 18 and ≤ 55 years.
  • BMI ≥ 18 and ≤27.
  • Informed consent, personally signed and dated to participate in the study.
  • ECOG performance status of 0-1.
  • Life expectancy of at least 12 weeks.
  • Total serum bilirubin ≤1.5×ULN.
  • Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5×ULN.
  • Serum creatinine ≤1.5×ULN.
  • glomerular filtration rate ≥60 mL/min, as calculated with the Cockcroft-Gault formula.
  • alkaline phosphatase ≤1.5×ULN.
  • urine protein ≤1+, or Urine protein was quantified for 24h ≤0.5g.
  • INR/PTT <1.5×ULN.

Exclusion Criteria:

  • Patients who are not eligible for standard chemotherapy as per discretion of the treating physician.
  • Patients who have been treated with bone marrow transplantation.
  • Central nervous system manifestation of AML.
  • Cardiac disease: heart failure NYHA III or IV; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
  • Patients who have thrombosis events within 6 months prior to study entry is permitted.
  • Pregnancy or breastfeed.
  • Chronic pulmonary disease with relevant hypoxia.
  • Patients undergoing dialysis.
  • Known HIV and/or hepatitis C infection.
  • Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy.
  • Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders.
  • Blood pressure (BP) higher than systolic 140 mmHg and/or diastolic 90 mmHg after best treatment.
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance of the protocol.
  • Patients with major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry is permitted.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Infection need antibiotic treatment.
  • Cumulative therapeutic dose of Daunorubicin more than 300mg/m2.
  • Concurrent malignancies other than AML.
  • History of organ allograft.
  • Allergy to study medication or excipients in study medication.

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: Non-Randomized
  • Interventional Model: Sequential 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: Donafenib, 0.2g
Donafenib,0.2g,bid,Combination with Cytarabine and Daunorubicin.
Drug: Donafenib
In first 28-days-cycle, eligible subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination with Daunorubicin 60mg/m2/d, for first 3 days, and Cytarabine 100mg/m2/d, for first 7 days. If CR or CRi is observed, subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination Cytarabine 2g/m2/q12h, for first 3 days, in next 28-day-cycle.
Other Names:
  • Cytarabine and Daunorubicin
Experimental: Donafenib,0.3g
Donafenib,0.3g,bid,Combination with Cytarabine and Daunorubicin
Drug: Donafenib
In first 28-days-cycle, eligible subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination with Daunorubicin 60mg/m2/d, for first 3 days, and Cytarabine 100mg/m2/d, for first 7 days. If CR or CRi is observed, subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination Cytarabine 2g/m2/q12h, for first 3 days, in next 28-day-cycle.
Other Names:
  • Cytarabine and Daunorubicin

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
Measure Description
Time Frame
Safety(including the type, severity and frequency of AE)
Time Frame: through study completion, an average of 2 months
Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.
through study completion, an average of 2 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.
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

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: Jianxiang Wang, Doctor, Institute of Hematology and Blood Disease Hospital

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 6, 2018

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.
February 9, 2022

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.
February 9, 2022

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).
May 18, 2020

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.
May 24, 2020

First Posted (Actual)

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.
May 27, 2020

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.
December 1, 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.
November 28, 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.
November 1, 2022

More Information

Terms related to this study

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.
  • ZGDAML1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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