LymphomaPhase 1NCT03786926
Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas
A Phase 1 study testing HMPL-689 in people with Lymphoma, run by Hutchmed at 27 sites in 6 countries.
Trial summary
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- HMPL-689
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 27 sitesin 6 countries
- Study dates
- 26 Aug 2019to 26 Jun 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- (ECOG) performance status of 0 or 1;
- Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);
- Patients with relapsed or refractory NHL for whom:
- Standard of care treatment options no longer exist (Stage 1 only);
- Standard of care treatment options no longer exist with the exception of PI3K-delta inhibitors (Stage 2 only);
- Expected survival of more than 24 weeks.
Who cannot join
- Patients who meet any of the following criteria will be excluded from study entry:
- Primary central nervous system (CNS) lymphoma;
- Any of the following laboratory abnormalities Absolute neutrophil count; <1.0×10^9/L, Hemoglobin <80 g/L Platelets <50 ×10^9/L
- Inadequate organ function, defined by the following:
- Total bilirubin ≥1.5 times the upper limit of normal (× ULN);
- AST or ALT > 2.5 × ULN;
Show all 27Show fewer
- Estimated creatinine clearance (CrCl) per Cockcroft-Gault;
- Dose Escalation stage of trial (Stage 1) - CrCl < 40 mL/min;
- Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min;
- International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;
- Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;
- Patients with presence of second primary malignant tumors within the last 2 years;
- Clinically significant history of liver disease;
- Prior treatment with any PI3Kδ inhibitors;
- Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within 7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment;
- Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);
- Major surgical procedure within 4 weeks prior to initiation of study treatment;
- Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;
- New York Heart Association (NYHA) Class II or greater congestive heart failure;
- Congenital long QT syndrome or QTc >470 msec;
- Currently use medication known to cause QT prolongation or torsades de pointes;
- History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;
- History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;
- Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;
- History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);
- Patients with ongoing chronic gastrointestinal diseases;
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
Trial locations and contacts
27 sites in 6 countries.
27 sites in 6 countries
United States10 sites
Innovative Clinical Research Institute
Anaheim, California, 92801
Pacific Cancer Medical Center
Anaheim, California, 92801
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Levine Cancer Institute- Atrium Health
Charlotte, North Carolina, 28204
Baylor Scott and White Research Institute
Dallas, Texas, 75246
Renovatio Clinical
Houston, Texas, 77339
Ventura County Hematology-Oncology Specialists
Oxnard, California, 93030
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Medical Oncology Associates, P.S.
Spokane, Washington, 99208
Clinical Research Alliance, Inc
Westbury, New York, 11590
Poland5 sites
KO-MED Centra Kliniczne
Biała Podlaska
Uniwersyteckie Centrum Kliniczne
Gdansk
BioResearch Group Sp. Z. o. o.
Krakow
NASZ LEKARZ Osrodek Badan Klinicznych
Torun
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego
Wroclaw, 50-566
Spain5 sites
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Barcelona
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona
Fundacion Jimenez Diaz
Madrid
Hospital Universitario Virgen del Rocio
Seville
Hospital Universitario Virgen Macarena
Seville
France3 sites
Hopital Henri Mondor
Créteil, Val De Marne, 94010
CHU de Nantes - Hotel Dieu
Nantes, 44000
CHU de Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604
Finland2 sites
Helsingin yliopistollinen keskussairaala
Helsinki, 00029
Tampereen yliopistollinen sairaala
Tampere, 33520
Italy2 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
Bologna
Ospedale San Raffaele
Milan
About this study
Official title: A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas
Read the detailed description
This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients with relapsed or refractory lymphoma.
HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling pathway
This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage (Stage 2).
Dose Escalation Stage (Stage 1):
This stage will end when any of the following criteria is met:
- The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities (DLTs) are observed out of the first 3 patients at dose level 1.
- The maximum sample size is reached.
- The MTD and/or RP2D is confirmed.
Dose Expansion Stage (Stage 2):
To further characterize the safety and explore the preliminary anti-tumor activity of HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.
- Conditions
- Lymphoma
- Being tested
- HMPL-689
- Keywords
- CLL, SLL, FL, MZL, LPL, WM, MCL, PTCL, CBCL
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-689Drug
HMPL-689 is a PI3Kδ inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | All patients take HMPL-689 taken daily Receives: Drug: HMPL-689 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)
A DLT was defined as the occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless equivocally due to underlying malignancy or an extraneous cause. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: non-hematologic toxicity: all non-hematologic TEAEs of grade 3 or greater with the exception of grade 3 nausea or vomiting that could be controlled by supportive therapy; hematologic toxicity: grade 4 neutropenia >5 days, grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding event or requiring platelet transfusion, grade >=3 febrile neutropenia (defined as absolute neutrophil count [ANC] <1000/cubic millimeter {mm^3} with a single temperature >38.3 degree Celsius [°C] or a sustained temperature of >=38°C for more than 1 hour), grade 4 anemia not explained by underlying disease; any TEAE that required a dose delay of >=15 days; any case of Hy's Law.
Measured: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)
Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)
An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. An SAE was an AE that resulted in any of the following: was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug, or was considered a significant medical event by the investigator. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs and SAEs were defined as AEs and SAEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.
Measured: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 34 months
Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events
An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs were defined as AEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.
Measured: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 27 months
Secondary outcomes (10)
Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)
ORR: percentage of patients with complete response (CR),CR with incomplete marrow recovery (CRi),nodular partial response (nPR),PR with lymphocytosis (PR-L) or PR for CLL patients; CR, very good PR (VGPR),PR or minor response (MR) for WM patients;CR or PR for patients with disease other than CLL and WM.CR: absence of serum (S) monoclonal immunoglobulin (Ig)M, normal S IgM, complete resolution of extramedullary disease,morphologically normal bone marrow aspirate and trephine biopsy. CRi:criteria fulfilled for CR but persistent cytopenia,anemia,thrombocytopenia or neutropenia. nPR:patients with residual CLL cells.PR-L:patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy.PR, VGPR, MR: detectable monoclonal IgM,no new signs/symptoms of active disease and PR: ≥50% but <90% reduction in S IgM,reduction in extramedullary disease,VGPR: >=90% reduction in S IgM,complete resolution of extramedullary disease,MR: >=25% but <50% reduction in S IgM.
Measured: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Time to Response (TTR)
TTR was defined as the time from the first dose of study drug to the first occurrence of CR, CRi, PR, nPR, VGPR, PR-L, or MR. CR: absence of serum monoclonal IgM, normal serum IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. PR: detectable monoclonal IgM, no new signs/symptoms of active disease, 50% but <90% reduction in serum IgM, reduction in extramedullary disease. nPR: patients with residual CLL cells. VGPR: detectable monoclonal IgM, no new signs/symptoms of active disease,>=90% reduction in serum IgM, complete resolution of extramedullary disease. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. MR: detectable monoclonal IgM, no new signs/symptoms of active disease, >=25% but <50% reduction in serum IgM.
Measured: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)
DOR: time from when first response (CR, CRi, PR, nPR, VGPR, PR-L and MR) was achieved until earlier of first documentation of definitive PD or death from any cause, whichever was earlier. CR: absence of S monoclonal IgM, normal S IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. nPR: patients with residual CLL cells. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. PR, VGPR, MR: detectable monoclonal IgM, no new signs/symptoms of active disease and PR: ≥50% but <90% reduction in S IgM, reduction in extramedullary disease, VGPR: >=90% reduction in S IgM, complete resolution of extramedullary disease, MR: >=25% but <50% reduction in S IgM. PD: >=25% increase in S IgM level from lowest nadir and/or progression in clinical features attributable to the disease.
Measured: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)
CBR was defined as percentage of patients who had best overall response (BOR) with stable disease (SD) or better. BOR was defined as the best response recorded from the start of treatment until PD or new anti-cancer therapy, whichever came earlier. PD: >=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease. SD: detectable monoclonal IgM, <25% reduction and <25% increase in serum IgM level, no progression in extramedullary disease, no new signs/symptoms of active disease.
Measured: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)
PFS was defined as the time from the date of first study drug to the earliest date of PD or death of any cause, whichever occurred first. PD was defined as >=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.
Measured: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months
Dose Escalation Stage: Plasma Concentration of HMPL-689
Blood samples were collected to determine plasma concentration of HMPL-689. The pharmacokinetic (PK) parameters were determined by non-compartmental analysis.
Measured: Pre-dose on Days 1, 2, 15, 16, 28 of Cycle 1 and on Day 1 of Cycle 2; 0.5, 1, 2, 4 and 8 hours post-dose on Days 1, 15 and 28 of Cycle 1 (each cycle is 28 days)
Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689
Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Measured: Days 1, 2, 15, 16, 28 of Cycle 1 and Day 1 of Cycle 2 (each cycle is 28 days)
Dose Expansion Stage: Plasma Concentration of HMPL-689
Blood samples were collected to determine plasma concentration of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Measured: Pre-dose on Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1; 0 hour on Day 1 of Cycle 1; 1, 2, 3, 4 hours post-dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)
Dose Expansion Stage: Plasma Trough Concentration of HMPL-689
Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Measured: Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1 (each cycle is 28 days)
Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)
12-lead electrocardiogram was performed to evaluate the effect of HMPL-689 on cardiac repolarization by detecting the changes in QTcF intervals. Baseline was defined as the last assessment performed prior to or on first non-zero dose date with time point marked as "pre-dose".
Measured: 2 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 2 and 4 hours on Day 15 of Cycle 1 (dose escalation phase); 1, 2, 3 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 1, 2, 3, and 4 hours on Day 15 of Cycle 1 (dose expansion phase) (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 posted26 Dec 2018
- Study start26 Aug 2019
- Primary completion26 Jun 2024
- Study completion26 Jun 2024
Why it stopped: 2018-689-00US1 has been halted by HUTCHMED based on strategic evaluation of the clinical development of HMPL-689 in the United States, Europe, and Australia.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by HutchmedThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Claudia Huang, Study director, Hutchmed LimitedNilanjan Ghosh, MD, Principal investigator, Atrium Health Levine Cancer InstituteJonathan B Cohen, MD, Principal investigator, Emory Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786926
- Sponsor's protocol ID
- 2018-689-00US1
- Status last verified
- Jun 2025
- First submitted
- 18 Dec 2018
- Last updated
- 26 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma
- ClinicalTrials.gov ID
- NCT03786926
- Acronym / sponsor ID
- 2018-689-00US1
- Conditions
- Lymphoma
- Keywords
- CLL, SLL, FL, MZL, LPL, WM, MCL, PTCL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 2018-689-00US1 has been halted by HUTCHMED based on strategic evaluation of the clinical development of HMPL-689 in the United States, Europe, and Australia.
- Enrolment
- 53 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 26 Aug 2019 (actual)
- Primary completion
- 26 Jun 2024 (actual)
- Study completion
- 26 Jun 2024 (actual)
- First posted
- 26 Dec 2018 (actual)
- Results
- Posted 26 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas
Detailed description
This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients with relapsed or refractory lymphoma.
HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling pathway
This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage (Stage 2).
Dose Escalation Stage (Stage 1):
This stage will end when any of the following criteria is met:
- The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities (DLTs) are observed out of the first 3 patients at dose level 1.
- The maximum sample size is reached.
- The MTD and/or RP2D is confirmed.
Dose Expansion Stage (Stage 2):
To further characterize the safety and explore the preliminary anti-tumor activity of HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: HMPL-689All patients take HMPL-689 taken daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- (ECOG) performance status of 0 or 1;
- Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);
- Patients with relapsed or refractory NHL for whom:
- Expected survival of more than 24 weeks.
Key exclusion criteria (27 listed)
- Primary central nervous system (CNS) lymphoma;
- Any of the following laboratory abnormalities Absolute neutrophil count; <1.0×10^9/L, Hemoglobin <80 g/L Platelets <50 ×10^9/L
- Inadequate organ function, defined by the following:
- International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;
- Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-689HMPL-689 is a PI3Kδ inhibitor | Drug | Treatment |
Primary outcome
Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)
Time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)
A DLT was defined as the occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless equivocally due to underlying malignancy or an extraneous cause. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: non-hematologic toxicity: all non-hematologic TEAEs of grade 3 or greater with the exception of grade 3 nausea or vomiting that could be controlled by supportive therapy; hematologic toxicity: grade 4 neutropenia >5 days, grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding event or requiring platelet transfusion, grade >=3 febrile neutropenia (defined as absolute neutrophil count [ANC] <1000/cubic millimeter {mm^3} with a single temperature >38.3 degree Celsius [°C] or a sustained temperature of >=38°C for more than 1 hour), grade 4 anemia not explained by underlying disease; any TEAE that required a dose delay of >=15 days; any case of Hy's Law.
Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)
Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 34 months
An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. An SAE was an AE that resulted in any of the following: was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug, or was considered a significant medical event by the investigator. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs and SAEs were defined as AEs and SAEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.
Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events
Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 27 months
An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs were defined as AEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.
10 secondary outcomes
Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)
Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Time to Response (TTR)
Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)
Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)
Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months
Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)
Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months
Dose Escalation Stage: Plasma Concentration of HMPL-689
Time frame: Pre-dose on Days 1, 2, 15, 16, 28 of Cycle 1 and on Day 1 of Cycle 2; 0.5, 1, 2, 4 and 8 hours post-dose on Days 1, 15 and 28 of Cycle 1 (each cycle is 28 days)
Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689
Time frame: Days 1, 2, 15, 16, 28 of Cycle 1 and Day 1 of Cycle 2 (each cycle is 28 days)
Dose Expansion Stage: Plasma Concentration of HMPL-689
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1; 0 hour on Day 1 of Cycle 1; 1, 2, 3, 4 hours post-dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)
Dose Expansion Stage: Plasma Trough Concentration of HMPL-689
Time frame: Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1 (each cycle is 28 days)
Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)
Time frame: 2 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 2 and 4 hours on Day 15 of Cycle 1 (dose escalation phase); 1, 2, 3 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 1, 2, 3, and 4 hours on Day 15 of Cycle 1 (dose expansion phase) (each cycle is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Cutaneous T-cell Lymphoma, Sezary Syndrome
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Huang study director
Hutchmed Limited
Nilanjan Ghosh, MD principal investigator
Atrium Health Levine Cancer Institute
Jonathan B Cohen, MD principal investigator
Emory Winship Cancer Institute
27 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMPL-689 in people with Lymphoma, run by Hutchmed at 27 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Poland, Spain, France, Finland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs) (time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.