A Clinical Trial to Evaluate Clifutinib in Patients with Relapsed or Refractory Acute Myeloid Leukemia(AML)

Sunshine Lake Pharma

Status and phase: Completed; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Clifutinib Besylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT04827069

PCD-DHEC73543-16-001

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of Clifutinib Besylate in Relapsed/refractory AML patients with FLT3-ITD mutation.

Full description

It is a multi-center , open-label, single arm study conducted in 2 parts. Dose-escalation part: Subjects will receive oral Clifutinib Besylate once on C0D1.After 3 days,they will receive Clifutinib Besylate once daily repeatedly until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days.

Expansion part:Expansion cohort might be set to further investigate the safety and efficacy of Clifutinib Besylate at or lower MTD dose recommended by dose-escalation part.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented acute myeloid leukemia according to World Health Organization（WHO） criteria(excluding acute promyelocytic leukemia), with FLT3-ITD gene mutation,refractory after common or enhanced chemotherapy or relapse.

• ECOG performance status of 0-1.

• Subjects must have adequate organ function and meeting all of the following laboratory review before enrollment：

  • Lood routine examination: WBC≤2000/mm3;
  • Liver function: Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤2.5×upper limit of normal(ULN); serum bilirubin ≤ 1.5 × ULN;
  • Renal function: Serum creatinine ≤ 1.5×ULN, or the creatinine clearance (CrCl)≥ 60 mL / min calculated by the Cockcroft-Gault formula;
  • Electrolyte: serum potassium≥3.0mmol/L; serum calcium≥2.0 mmol/L;serum magnesium≥0.5 mmol/L;
  • Coagulation function:fibrinogen≥1.0g/L; activated partial thromboplastin time( APTT)≦ULN+10s; prothrombin time(PT)≤ULN+3s.

Exclusion criteria

• Received FLT3 inhibitors within 4 weeks prior to the administration;
• Received hematopoietic stem cell transplantation within2 months prior to the administration or received immunosuppressor beceause of GVHD;
• Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to administration;
• Nitrosourea and mitomycin chemotherapy within 6 weeks prior to the administration;
• Have taken live vaccines within 4 weeks prior to /or concurrent with the administration;
• Have received a trial investigational product, or participated in other clinical trials within 4 weeks prior to administration;
• Documented promyelocytic leukemia (t (15; 17) (q22; q11) and / or promyelocytic leukemia(PML)/retinoic acid receptor alpha (RARa) positivity found in the chromosome, variant acute promyelocytic leukemia;
• With myeloid sarcoma or invasion of central nervous system;
• NCI CTCAE 4.03 ≥ 2 grade of arrhythmia, or corrected QT interval(QTc )> 450 ms ; patients with a history of torsion or congenital QT prolonged syndrome; active infectious disease judged by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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75 participants in 6 patient groups

Arm 1

Experimental group

Description:

Clifutinib Besylate:10 mg

Treatment:

Drug: Clifutinib Besylate

Arm 2

Experimental group

Description:

Clifutinib Besylate:20 mg

Treatment:

Drug: Clifutinib Besylate

Arm 3

Experimental group

Description:

Clifutinib Besylate:40 mg

Treatment:

Drug: Clifutinib Besylate

Arm 4

Experimental group

Description:

Clifutinib Besylate:55 mg

Treatment:

Drug: Clifutinib Besylate

Arm 5

Experimental group

Description:

Clifutinib Besylate:70 mg

Treatment:

Drug: Clifutinib Besylate

Arm 6

Experimental group

Description:

Clifutinib Besylate:100 mg

Treatment:

Drug: Clifutinib Besylate