A Phase 1 Clinical Trail of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies

Relapsed/Refractory Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Preliminary Efficacy of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06049667
• Other study ID #: NTQ2494-23101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 7, 2023
• Est. completion date: August 2026

Study information

• Verified date: September 2023
• Source: Nanjing Chia-tai Tianqing Pharmaceutical
• Contact: Yu meng Zhou
• Phone: 86-025-85109999
• Email: yumeng_zhou[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

NTQ2494 tablet, an anti-tumor molecular targeted drug, is an AXL kinase inhibitor. The objectives were to evaluate the safety and tolerability, PK characteristics and preliminary efficacy of NTQ2494 tablets in patients with advanced hematological malignancies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: August 2026
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. =18 years in age, male or female.

2. Relapsed/refractory AML patients.

3. ECOG performance status score is 0 to 2.

4. Life expectancy of at least 3 months.

5. Adequate bone marrow and good organ function.

6. Ability to understand the purpose and risks of the study and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Receiving anticancer therapy including immunotherapy, targeted therapy, endocrine therapy, radiotherapy and chemotherapy within 2 weeks or 5 half-lives (whichever is longer) prior to starting study treatment.

2. Receiving any other investigational agents within 4 weeks prior to starting study treatment.

3. Having major surgery within 4 weeks prior to starting study treatment, or intended to undergo surgery during the trail.

4. AML with any of the following: 1) acute promyelocytic leukemia; 2) AML with blast crisis of chronic myelogenous leukemia; 3) central nervous system leukemia.

5. Prior or current other malignancy (except cured noninvasive basal cell or squamous cell skin cancer and/or other cured carcinoma in situ; except for other malignancies that have achieved clinical cure for > 5 years and have not recurred within 5 years).History of severe cardiovascular or cerebrovascular disease.

6. Use of strong inhibitors or strong inducers of CYP3A4 or P-gp within 7 days prior to starting study treatment.

7. Receiving (attenuated) live vaccines within 4 weeks prior to starting study treatment and/or planning to receive (attenuated) live vaccines during the trial.

8. With unresolved clinically significant non-hematological toxicities from prior AML therapy (chemotherapy, targeted therapy, immunotherapy, radiotherapy and surgery), defined as any grade 2 or higher grade (CTCAE v5.0), alopecia and other events that are tolerable as judged by the investigator.

9. Patients who have received previous allogeneic hematopoietic stem cell transplantation; or received autologous hematopoietic stem cell transplantation within 3 months prior to starting study treatment.

10. Unable to swallow oral tablets, or other conditions seriously affecting gastrointestinal absorption judged by the investigator.

11. Patients with uncontrolled infections unsuitable for the trail judged by the investigator.

12. Known infection with hepatitis B, hepatitis C, HIV or Syphilis.

13. Known alcohol or drug dependence.

14. Patients with mental disorders or poor compliance.

15. Patients with a previous history of severe allergy to any drug or food.

16. Lactating or pregnant female, and females or males (or partners) who plan to pregnant and do not agree to use adequate contraception for the duration of the trail and up to 3 months after completion of the last study treatment.

17. Other reasons judged by the investigator that the patients unsuitable for the trail.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia, Myeloid, Acute
• Relapsed/Refractory Acute Myeloid Leukemia (AML)

Intervention

Drug:
• NTQ2494 tablet
Drug: NTQ2494 tablet Part 1: Dose escalation, single and multiple doses of NTQ2494 with dose modifications based on tolerability criteria. For each dose level, a single dose of NTQ2494 tablets will be first administered orally, then continuous 28-day treatment will start (per cycle). Part 2: Dose expansion, recommended doses from Part 1. For each dose level, multiple doses of NTQ2494 tablets will be administered as 28-day treatment (per cycle).

Locations

Country	Name	City	State
China	Hematology Hospital of the Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing Chia-tai Tianqing Pharmaceutical

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerance dose (MTD) and dose limiting toxicity (DLT)	MTD is defined as the maximum dose level at which no more than 1 of 3 participants experience a DLT within the days of single dose and the first 28 days of multiple doses in dose escalation part.	30 days
Secondary	Cmax of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	AUC0-t of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	AUC0-8 of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Tmax of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	t1/2z of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Vz/F of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	CLz/F of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	?z of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	MRT0-t of single dose		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Rac of AUC and Cmax of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	DF of AUC and Cmax of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Css,max of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Css,min of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	AUCss of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Cav of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Tss,max of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	t1/2 of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Vz/F of first 28 days of multiple doses	?Vz/F?CLss/F??z of first 28 days of multiple doses.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	CLss/F of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	?z of first 28 days of multiple doses		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Objective response rate (ORR)	ORR is defined as the proportion of subjects with confirmed CRc or PR.	through study completion, an average of 1 year
Secondary	Composite response (CRc) rate	CRc rate is defined as the proportion of subjects with confirmed CR or CRi or CRh.	through study completion, an average of 1 year
Secondary	Duration of response (DOR)	DOR is defined as the duration from the date of the first documented response of CR or PR to the date of the first documented recurrence or death.	through study completion, an average of 1 year
Secondary	Recurrence-free survival (RFS)	RFS is defined as the duration from the date of the first documented response of CRc to the date of the first documented recurrence or death.	through study completion, an average of 1 year