Hematologic MalignancyPhase 1/2NCT06206174
TGRX-814 Chinese Phase I/II in Patients With Hematological Malignancies
A Phase 1/2 study testing TGRX-814 in people with Hematologic Malignancy and Non Hodgkin Lymphoma, run by Shenzhen TargetRx Co., Ltd. at 1 site in China.
Trial summary
The purpose of this single- arm, open-label, dose escalation and dose expansion phase I/II study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-814 in patients with hematological malignancies including non-Hodgkin lymphoma, acute myeloid leukemia, aute lymphoblastic leukemia… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy, Non Hodgkin Lymphoma, Acute Myeloid Leukemia
- What is being tested?
- TGRX-814
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 6 Mar 2024to 28 Feb 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female ≥ 18 years of age
- fully understand the requirements of the study and voluntarily sign a written informed consent form
- diagnosis of NHL, ALL, AML or MDS
- Eastern Cooperative Oncology Group (ECOG) physical status score ≤ 2
- adequate bone marrow function
- patients at high risk for Tumor Lysis Syndrome (TLS) determined by investigator and sponsor for agreement to enroll
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- adequate disease indicator
- adequate coagulation, hepatic and renal function
- female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use a medically approved highly effective contraceptive from the time of signing the Informed Consent Form until at least 3 months after the last dose of study drug; women of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose of study drug
- Expected survival time ≥ 12 weeks
Who cannot join
- received BCL-2 inhibitor therapy prior to the first dose of study drug, unless discontinued due to intolerance
- subjects with NHL have been diagnosed with Burkitt's lymphoma, lymphoblastoid lymphoma/leukemia, or post-transplant lymphoproliferative disease (PTLD)
- AML subjects with a diagnosis of acute promyelocytic leukemia or Ph chromosome positive or persistent extramedullary leukemia
- tumor infiltration of the central nervous system
- received allogeneic hematopoietic stem cell transplantation; or received autologous hematopoietic stem cell transplantation within 3 months
- received vaccination within 4 weeks prior to first dose or scheduled to be vaccinated during the study
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- HBsAg-positive or HBcAb-positive; HCV antibody-positive; HIV antibody-positive
- monoclonal antibody antitumor therapy within 4 weeks prior to the first dose; participation in a clinical trial of another interventional drug within 4 weeks prior to the first dose; participation in CAR-T therapy within 12 weeks prior to the first dose; 9. 14 weeks prior to the first dose
- received anticancer therapy/investigational therapy within 14 days prior to the first dose, or has not recovered from clinically significant toxicity below grade 2 on prior therapy
- received steroidal anticancer therapy, CYP3A inhibitors, or CYP3A inducers within 7 days prior to the first dose of study drug
- consumption of grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or popcorn within 3 days prior to the first dose of the drug
- poorly controlled hypertension; left ventricular ejection fraction ≤ 50% as assessed by cardiac ultrasound; prolonged QT interval; Grade III atrioventricular block or other arrhythmia requiring medical intervention; New York Heart Association (NYHA) Class III or IV congestive heart failure; had myocardial infarction or experienced bypass surgery within 6 months prior to dosing; had arterial or venous thrombotic events within 6 months prior to the first dose of study drug; have other cardiovascular diseases that investigator deemed unfit for enrollment
- having a history of renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect the subject's participation in this study
- having a history of active malignancy other than NHL, AML, or MDS within 3 years prior to participation in this clinical study
- having a condition of malabsorption syndrome or multiple factors that interfere with the oral administration and absorption of medication
- other uncontrolled conditions of clinical significance
- other factors that, in the opinion of the Investigator, may affect the results of the study and interfere with the patient's participation in the study, including previous or existing medical conditions, abnormalities in treatment or laboratory tests, unwillingness of the subject to comply with the procedures, restrictions and requirements of the study, and other conditions that make enrollment in the study unsuitable.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, 300020
Jianxiang Wang, MD, +86-022-23909120, wangjx@ihcams.ac.cn
About this study
Official title: A Single-arm, Open-label, Dose Escalation and Expansion Phase I/II Study Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TGRX-814 Monotherapy and Combination Therapy in Patients With Hematological Malignancies
The purpose of this single- arm, open-label, dose escalation and dose expansion phase I/II study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-814 in patients with hematological malignancies including non-Hodgkin lymphoma, acute myeloid leukemia, aute lymphoblastic leukemia and myelodysplastic syndromes.
Read the detailed description
This is the first-in-human trial with TGRX-814 which aims to evaluate the safety, pharmacokinetic and preliminary efficacy profiles with hematological malignancies. The primary purpose of this study is to evaluate the safety profile of TGRX-814 in patients with non-Hodgkin lymphoma and to determine of the maximal tolerated dose (MTD) and recommended phase II dose (RP2D). Other purposes of the study include evaluating safety and preliminary efficacy of TGRX-814 monotherapy and combination therapy in patients with other types of hematological malignancies, including acute myeloid leukemia, aute lymphoblastic leukemia and myelodysplastic syndromes, as well as evaluating the pharmacokinetic profile of TGRX-814. The study is a phase I/II study, consisting a monotherapy dose escalation study, monotherapy dose expansion study and combination therapy study.
- Conditions
- Hematologic Malignancy, Non Hodgkin Lymphoma, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Adult, Myelodysplastic Syndromes
- Being tested
- TGRX-814
- Medical subject headings
- Hematologic Neoplasms, Lymphoma, Non-Hodgkin, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGRX-814Drug
Also called TGRX-814 monotherapy
Participants are given TGRX-814 tablets for oral, once daily administration at one of the dose levels as pre-determined for the dose escalation sequence.
| Study group | Role | What they receive |
|---|---|---|
| TGRX-814 | Experimental | TGRX-814 monotherapy for Dose escalation study; oral, once daily administration. Receives: Drug: TGRX-814 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MTD)
To determine the MTD of TGRX-814 in non-Hodgkin lymphoma (NHL) patients
Measured: At end of dose escalation when the probability of DLT of a dose level is greater than 0.359
Recommended phase II dose (RP2D)
To determine the RP2D of TGRX-814 in NHL patients for Phase II
Measured: At completion of the dose escalation study, an average of 1 year
Secondary outcomes (23)
Dose-limiting toxicities (DLTs)
to record and analyze DLTs in all patients with hematological malignancies
Measured: DLT is collected during Cycle 1 (each cycle is 28 days)
Adverse Events (AEs)/Serious Adverse Events (SAEs)
to record and analyze AEs/SAEs in all patients with hematological malignancies
Measured: AE and SAE are collected throughout and until completion of the study, an average of 1 year.
Complete Response (CR) rate
to record and analyze the CR rate in patients with NHL, ALL, AML, and MDS
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Complete response with incomplete count recovery (CRi) rate
to record and analyze the CRi rate in patients with NHL, ALL, and AML
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Partial response (PR) rate
to record and analyze the PR rate in patients with NHL, AML, and MDS
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Partial response with lymphocytosis (PRL) rate
to record and analyze the PRL rate in patients with NHL
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Stable disease (SD) rate
to record and analyze the SD rate in patients with NHL
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Objective response rate (ORR)
to record and analyze the ORR in patients with NHL
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Duration of complete response (DCR)
to record and analyze the DCR in patients with NHL and AML
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Duration of response (DOR)
to record and analyze the DOR in patients with NHL, ALL, AML and MDS
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Overall Survival (OS) rate
to record and analyze the OS rate in patients with NHL, ALL, AML and MDS
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Morphologic leukemia-free state (MLFS) rate
to record and analyze the MLFS rate in patients with ALL and AML
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Complete response with partial hematologic recovery (CRh)
to record and analyze the CRh rate in patients with ALL
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Molecular complete response (mCR) rate
to record and analyze the mCR rate in patients with MDS
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Progress-Free survival (PFS) rate
to record and analyze the PFS rate in patients withAML
Measured: at screening period, at the end of week 8, 16, 24, 36, 48, subsequent every 24 weeks and the last visit of treatment period, at the end-of-treatment follow-up visit and safety follow-up visit
Minimum concentration at steady state (Css-min)
to measure/calculate the Pharmacokinetic (PK) parameter of Css-min in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Maximum concentration at steady state (Css-max)
to measure/calculate the PK parameter of Css-max in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Average concentration at steady state (Css-ave)
to measure/calculate the PK parameter of Css-ave in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Time of Maximum concentration at steady state (Tmax,ss)
to measure/calculate the PK parameter of Tmax,ss in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Area-under-curve in treatment interval at steady state (AUCtau-ss)
to measure/calculate the PK parameter of AUCtau-ss in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Volume of distribution at steady state (Vss)
to measure/calculate the PK parameter of Vss in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Accumulation ratio (AR)
to measure/calculate the PK parameter of AR in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Degree of fluctuation (DF)
to measure/calculate the PK parameter of DF in all patients with hematological malignancy
Measured: at screening period, and at day 1, 15 and 22 of Cycle 1, day 1 of Cycle 3, day 1 of Cycle 5, and day 1 of Cycle 7 of the treatment period (each Cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2024
- Study start6 Mar 2024
- Primary completion28 Feb 2025 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen TargetRx Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Institute of Hematology & Blood Diseases Hospital, China
- Responsible party
- Sponsor
- Investigators
- Jianxiang Wang, MD, Principal investigator, Institute of Hematology & Blood Diseases Hospital, ChinaBo Jiang, MD, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06206174
- Sponsor's protocol ID
- TGRX-814-1001
- Status last verified
- Apr 2024
- First submitted
- 4 Jan 2024
- Last updated
- 10 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No