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

Primary Purpose

Relapsed/Refractory Acute Myeloid Leukemia (AML)

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
NTQ2494 tablet
Sponsored by
Nanjing Chia-tai Tianqing Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ≥18 years in age, male or female. Relapsed/refractory AML patients. ECOG performance status score is 0 to 2. Life expectancy of at least 3 months. Adequate bone marrow and good organ function. Ability to understand the purpose and risks of the study and the willingness to sign a written informed consent document. Exclusion Criteria: 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. Receiving any other investigational agents within 4 weeks prior to starting study treatment. Having major surgery within 4 weeks prior to starting study treatment, or intended to undergo surgery during the trail. AML with any of the following: 1) acute promyelocytic leukemia; 2) AML with blast crisis of chronic myelogenous leukemia; 3) central nervous system leukemia. 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. Use of strong inhibitors or strong inducers of CYP3A4 or P-gp within 7 days prior to starting study treatment. Receiving (attenuated) live vaccines within 4 weeks prior to starting study treatment and/or planning to receive (attenuated) live vaccines during the trial. 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. 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. Unable to swallow oral tablets, or other conditions seriously affecting gastrointestinal absorption judged by the investigator. Patients with uncontrolled infections unsuitable for the trail judged by the investigator. Known infection with hepatitis B, hepatitis C, HIV or Syphilis. Known alcohol or drug dependence. Patients with mental disorders or poor compliance. Patients with a previous history of severe allergy to any drug or food. 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. Other reasons judged by the investigator that the patients unsuitable for the trail.

Sites / Locations

  • Hematology Hospital of the Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NTQ2494

Arm Description

For each dose level, multiple doses of NTQ2494 tablets will be administered as 28-day treatment (per cycle).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Cmax of single dose
AUC0-t of single dose
AUC0-∞ of single dose
Tmax of single dose
t1/2z of single dose
Vz/F of single dose
CLz/F of single dose
λz of single dose
MRT0-t of single dose
Rac of AUC and Cmax of first 28 days of multiple doses
DF of AUC and Cmax of first 28 days of multiple doses
Css,max of first 28 days of multiple doses
Css,min of first 28 days of multiple doses
AUCss of first 28 days of multiple doses
Cav of first 28 days of multiple doses
Tss,max of first 28 days of multiple doses
t1/2 of first 28 days of multiple doses
Vz/F of first 28 days of multiple doses
、Vz/F、CLss/F、λz of first 28 days of multiple doses.
CLss/F of first 28 days of multiple doses
λz of first 28 days of multiple doses
Objective response rate (ORR)
ORR is defined as the proportion of subjects with confirmed CRc or PR.
Composite response (CRc) rate
CRc rate is defined as the proportion of subjects with confirmed CR or CRi or CRh.
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.
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.

Full Information

First Posted
September 11, 2023
Last Updated
September 17, 2023
Sponsor
Nanjing Chia-tai Tianqing Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT06049667
Brief Title
A Phase 1 Clinical Trail of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 7, 2023 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanjing Chia-tai Tianqing Pharmaceutical

4. Oversight

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

5. Study Description

Brief 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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NTQ2494
Arm Type
Experimental
Arm Description
For each dose level, multiple doses of NTQ2494 tablets will be administered as 28-day treatment (per cycle).
Intervention Type
Drug
Intervention Name(s)
NTQ2494 tablet
Intervention Description
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).
Primary Outcome Measure Information:
Title
Maximum tolerance dose (MTD) and dose limiting toxicity (DLT)
Description
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.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Cmax of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
AUC0-t of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
AUC0-∞ of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Tmax of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
t1/2z of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Vz/F of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
CLz/F of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
λz of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
MRT0-t of single dose
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Rac of AUC and Cmax of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
DF of AUC and Cmax of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Css,max of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Css,min of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
AUCss of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Cav of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Tss,max of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
t1/2 of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Vz/F of first 28 days of multiple doses
Description
、Vz/F、CLss/F、λz of first 28 days of multiple doses.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
CLss/F of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
λz of first 28 days of multiple doses
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Objective response rate (ORR)
Description
ORR is defined as the proportion of subjects with confirmed CRc or PR.
Time Frame
through study completion, an average of 1 year
Title
Composite response (CRc) rate
Description
CRc rate is defined as the proportion of subjects with confirmed CR or CRi or CRh.
Time Frame
through study completion, an average of 1 year
Title
Duration of response (DOR)
Description
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.
Time Frame
through study completion, an average of 1 year
Title
Recurrence-free survival (RFS)
Description
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.
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years in age, male or female. Relapsed/refractory AML patients. ECOG performance status score is 0 to 2. Life expectancy of at least 3 months. Adequate bone marrow and good organ function. Ability to understand the purpose and risks of the study and the willingness to sign a written informed consent document. Exclusion Criteria: 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. Receiving any other investigational agents within 4 weeks prior to starting study treatment. Having major surgery within 4 weeks prior to starting study treatment, or intended to undergo surgery during the trail. AML with any of the following: 1) acute promyelocytic leukemia; 2) AML with blast crisis of chronic myelogenous leukemia; 3) central nervous system leukemia. 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. Use of strong inhibitors or strong inducers of CYP3A4 or P-gp within 7 days prior to starting study treatment. Receiving (attenuated) live vaccines within 4 weeks prior to starting study treatment and/or planning to receive (attenuated) live vaccines during the trial. 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. 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. Unable to swallow oral tablets, or other conditions seriously affecting gastrointestinal absorption judged by the investigator. Patients with uncontrolled infections unsuitable for the trail judged by the investigator. Known infection with hepatitis B, hepatitis C, HIV or Syphilis. Known alcohol or drug dependence. Patients with mental disorders or poor compliance. Patients with a previous history of severe allergy to any drug or food. 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. Other reasons judged by the investigator that the patients unsuitable for the trail.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu meng Zhou
Phone
86-025-85109999
Email
yumeng_zhou@163.com
Facility Information:
Facility Name
Hematology Hospital of the Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jianxiang wang
First Name & Middle Initial & Last Name & Degree
jianxiang wang

12. IPD Sharing Statement

Learn more about this trial

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

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