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

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

8

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

  • 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

Ages Eligible for Study

16 years to 53 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
Intervention / Treatment
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

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

Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Investigators

  • 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)

November 6, 2018

Primary Completion (Actual)

February 9, 2022

Study Completion (Actual)

February 9, 2022

Study Registration Dates

First Submitted

May 18, 2020

First Submitted That Met QC Criteria

May 24, 2020

First Posted (Actual)

May 27, 2020

Study Record Updates

Last Update Posted (Actual)

December 1, 2022

Last Update Submitted That Met QC Criteria

November 28, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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