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Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Donafenib
Sponsored by
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML)

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Institute of Hematology and Blood Disease Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Donafenib, 0.2g

Donafenib,0.3g

Arm Description

Donafenib,0.2g,bid,Combination with Cytarabine and Daunorubicin.

Donafenib,0.3g,bid,Combination with Cytarabine and Daunorubicin

Outcomes

Primary Outcome Measures

Safety(including the type, severity and frequency of AE)
Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.

Secondary Outcome Measures

Full Information

First Posted
May 18, 2020
Last Updated
November 28, 2022
Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04402723
Brief Title
Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML
Official Title
A Dose-escalated Phase Ⅰ Trial to Assess the Tolerance and Pharmacokinetics of Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML Patient
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Corporate policy adjustments
Study Start Date
November 6, 2018 (Actual)
Primary Completion Date
February 9, 2022 (Actual)
Study Completion Date
February 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Donafenib, 0.2g
Arm Type
Experimental
Arm Description
Donafenib,0.2g,bid,Combination with Cytarabine and Daunorubicin.
Arm Title
Donafenib,0.3g
Arm Type
Experimental
Arm Description
Donafenib,0.3g,bid,Combination with Cytarabine and Daunorubicin
Intervention Type
Drug
Intervention Name(s)
Donafenib
Other Intervention Name(s)
Cytarabine and Daunorubicin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety(including the type, severity and frequency of AE)
Description
Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.
Time Frame
through study completion, an average of 2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang, Doctor
Organizational Affiliation
Institute of Hematology and Blood Disease Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology and Blood Disease Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China

12. IPD Sharing Statement

Learn more about this trial

Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML

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