Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML

NCT04402723 | Terminated Phase 1 DMC

• 1 other identifier: ZGDAML1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Safety(including the type, severity and frequency of AE)

  Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.

  through study completion, an average of 2 months

Study Arms (2)

Donafenib, 0.2g

EXPERIMENTAL

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

Drug: Donafenib

Donafenib,0.3g

EXPERIMENTAL

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

Drug: Donafenib

Interventions

Donafenib DRUG

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.

Also known as: Cytarabine and Daunorubicin

Donafenib, 0.2g; Donafenib,0.3g

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

Institute of Hematology and Blood Disease Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

donafenib; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Jianxiang Wang, Doctor

  Institute of Hematology and Blood Disease Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 27, 2020
• Study Start: November 6, 2018
• Primary Completion: February 9, 2022
• Study Completion: February 9, 2022
• Last Updated: December 1, 2022

Record last verified: 2022-11

Locations

CN (1)