CLL/SLLPhase 1NCT05176691
HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL
A Phase 1 study testing HMPL-760 in people with CLL/SLL and NHL, run by Hutchmed at 36 sites in 7 countries.
Trial summary
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- HMPL-760
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 36 sitesin 7 countries
- Study dates
- 15 Feb 2022to 16 Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 NHL or CLL with disease progression or intolerance to either ≥2 prior regimens. Patients with CLL/SLL and indolent NHL must meet criteria for systemic therapy. Patients with gastric extranodal MZL who are H. pylori positive must have failed H. pylori eradication therapy.
- Availability of tumor sample: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available for patients in dose escalation, the Sponsor may waive the requirement after discussion.
- Dose expansion stage only: Patients must have been treated with 1 prior regimen containing a BTK inhibitor in cohorts 1 to 5;
- Expected survival of more than 24 weeks as determined by the Investigator.
Who cannot join
- Patients with primary central nervous system lymphoma.
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) <0.75×109/L
- Hemoglobin <8 mg/L
- Platelets <50×109/L
- Note: In the dose expansion stage, patients with cell counts below the thresholds listed above may be considered eligible if there is documented bone marrow infiltration and Sponsor approval
Show all 26Show fewer
- Inadequate organ function
- International normalized ratio (INR) >1.5×ULN, activated partial thromboplastin time (aPTT) >1.5×ULN
- Patients requiring anticoagulation therapy (except vitamin K antagonists [ie, warfarin]) but with a stable INR within the recommended range according to the local guideline are eligible.
- Patients with presence of second primary malignant tumors within the last 2 years, with the exception of the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Clinically significant history of liver disease, including cirrhosis or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV).
- Cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to initiation of study treatment. For oral targeted therapies, a washout period of 5 half-lives of the agent (minimum 3 days) prior to the initiation of study treatment can be used.
- Any granulocyte colony-stimulating factor treatment/blood transfusion within 7 days before the screening hematology test.
- Prior use of any drug that is a strong inducer or inhibitor of CYP3A4 within 2 weeks prior to initiation of study treatment.
- Prior use of proton pump inhibitors (PPIs) within 5 days of study treatment
- Any transplant within 100 days prior to initiation of study treatment
- Clinically significant active infection or with an unexplained fever.
- Treatment within a clinical study of an investigational agent or using an investigational device within 3 weeks prior to initiation of the current study treatment.
- AEs from prior antineoplastic therapy that have not resolved to grade <1
- Pregnant (positive urine or serum beta human chorionic gonadotropin test) or lactating women.
- New Your Heart Association (NYHA) class II or greater congestive heart failure.
- NOTE: Only key inclusion/exclusion criteria are listed. Full details are in the protocol.
Trial locations and contacts
36 sites in 7 countries.
36 sites in 7 countries
United States12 sites
Innovative Clinical Research
Anaheim, California, 92801
Emory University Hospital
Atlanta, Georgia, 30322
Johns Hopkins Clinical Research Center
Baltimore, Maryland, 21287
Renovatio Clinical
El Paso, Texas, 79915
Summit Medical Group
Florham Park, New Jersey, 07932
Oncology Consultants, P.A.
Houston, Texas, 77030
AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company
Kansas City, Missouri, 64114
Tulane Cancer Center
New Orleans, Louisiana, 70112
New York University Langone Med Center. Lab
New York, New York, 10016
Center For Advanced Medicine
St Louis, Missouri, 63110
Renovatio Clinical
The Woodlands, Texas, 79915
Clinical Research Alliance
Westbury, New York, 11590
Spain6 sites
Hospital del Mar
Barcelona, 8003
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, 8908
MD Anderson Cancer Centre
Madrid, 28033
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Universitario Virgen del Rocio
Seville, Sevilla, 41010
France5 sites
Centre Antoine Lacassagne
Nice, Alpes Maritimes, 6200
Hôpital Saint-Antoine
Paris, Paris, 7551
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 75651
CHU Poitiers - Hôpital la Milétrie
Poitiers, Vienne, 86021
Institut Gustave Roussy
Villejuif, Val De Marne, 94805
Israel4 sites
Hadassah University Hospital - Ein Kerem
Jerusalem, 9112001
Rabin Medical Center-Beilinson Campus
Petah Tikva, 4941492
Chaim Sheba Medical Center
Ramat Gan, 5262001
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
Italy4 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
Bologna, 40138
Fondazione del Piemonte per l'Oncologia IRCC Candiolo
Candiolo, Torino, 10060
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Lazio, Roma, 168
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
Milan, 20122
Poland4 sites
Pratia Onkologia Katowice
Katowice, 40-519
Wojewodzki Szpital Specjalistyczny w Legnicy
Legnica, 59-220
Centrum Medyczne Pratia Poznan
Skórzewo, 60-185
MICS Centrum Medyczne Torun
Torun, 87-100
About this study
Official title: A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL)
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
Read the detailed description
HMPL-760 is a highly potent, selective, and reversible inhibitor against BTK, which would be studied in B-cell malignancy carrying either BTK(WT) or BTK(C481S).
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
The study consists of 2 parts:
Part 1- Dose Escalation to determine MTD and/or RP2D of HMPL-760
Part 2- Dose Expansion to characterize the safety and tolerability of HMPL-760
- Conditions
- CLL/SLL, NHL, MCL, MZL, Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
- Being tested
- HMPL-760
- Keywords
- Lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia, Chronic lymphocytic leukemia, Non-Hodgkin lymphoma, Mantle cell lymphoma, Marginal zone lymphoma, Follicular lymphoma, Diffuse large B-cell lymphoma, BTK inhibitor
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-760Drug
Administered orally QD for 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | All patients to receive HMPL-760 daily. Receives: Drug: HMPL-760 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs
Adverse event (AE) that meets protocol defined DLT criteria during dose escalation
Measured: Up to 28 days after first dose of study drug
Incidence of AEs/SAEs
Any untoward medical occurrence associated with the use of study drug
Measured: From 1st dose to within 30 days of last dose
MTD
To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached
Measured: From 1st dose to within 30 days of last dose
RP2D
To determine recommended phase 2 dose of HMPL-760 in subjects
Measured: From 1st dose to within 30 days of last dose
Secondary outcomes (7)
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects achieving partial response and better response during the study
Measured: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Duration of Response (DoR)
DoR is defined as the time between the initial response to therapy and subsequent disease progression or relapse.
Measured: From first dose of study drug to the time of progressive disease, assessed up to 36 months
Clinical Benefit Rate (CBR)
CBR is defined as the proportion of subjects achieving objective response or stable disease
Measured: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Progression-free Survival (PFS)
PFS is defined as survival without progression of the disease
Measured: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Maximum Plasma Concentration [Cmax]
To determine the maximum observed plasma concentration of HMPL-760
Measured: From 1st dose to within 30 days of last dose
Chemokines
To observe blood plasma concentrations of chemokines such as CCL22 and CCL3
Measured: From 1st dose to within 30 days of last dose
Phospho-BTK
To observe the whole blood concentrations of phospho-BTK
Measured: From 1st dose to within 30 days of last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study start15 Feb 2022
- Primary completion16 Nov 2022
- Study completion16 Nov 2022
Why it stopped: HUTCHMED has decided to discontinue the HMPL 760 study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CLL/SLLStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vijay Jayaprakash, MBBS, PHD, Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05176691
- Sponsor's protocol ID
- 2021-760-GLOB1
- Status last verified
- Feb 2023
- First submitted
- 19 Nov 2021
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT05176691
- Acronym / sponsor ID
- 2021-760-GLOB1
- Conditions
- CLL/SLL, NHL, MCL, MZL, Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
- Keywords
- Lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia, Chronic lymphocytic leukemia, Non-Hodgkin lymphoma, Mantle cell lymphoma, Marginal zone lymphoma, Follicular lymphoma, Diffuse large B-cell lymphoma, BTK inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: HUTCHMED has decided to discontinue the HMPL 760 study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 16 Nov 2022 (actual)
- Study completion
- 16 Nov 2022 (actual)
- First posted
- 4 Jan 2022 (actual)
- Results
- Not posted in the source record
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 single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
Detailed description
HMPL-760 is a highly potent, selective, and reversible inhibitor against BTK, which would be studied in B-cell malignancy carrying either BTK(WT) or BTK(C481S).
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
The study consists of 2 parts:
Part 1- Dose Escalation to determine MTD and/or RP2D of HMPL-760
Part 2- Dose Expansion to characterize the safety and tolerability of HMPL-760
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-760All patients to receive HMPL-760 daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ECOG performance status of 0 or 1;
- Histologically confirmed NHL or CLL with disease progression or intolerance to either ≥2 prior regimens. Patients with CLL/SLL and indolent NHL must meet criteria for systemic therapy. Patients with gastric extranodal MZL who are H. pylori positive must have failed H. pylori eradication therapy.
- Availability of tumor sample: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available for patients in dose escalation, the Sponsor may waive the requirement after discussion.
- Dose expansion stage only: Patients must have been treated with 1 prior regimen containing a BTK inhibitor in cohorts 1 to 5;
- Expected survival of more than 24 weeks as determined by the Investigator.
Key exclusion criteria (26 listed)
- Patients with primary central nervous system lymphoma.
- Any of the following laboratory abnormalities:
- Inadequate organ function
- International normalized ratio (INR) >1.5×ULN, activated partial thromboplastin time (aPTT) >1.5×ULN
- Patients with presence of second primary malignant tumors within the last 2 years, with the exception of the following:
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-760Administered orally QD for 28-day cycles | Drug | Treatment |
Primary outcome
Incidence of DLTs
Time frame: Up to 28 days after first dose of study drug
Adverse event (AE) that meets protocol defined DLT criteria during dose escalation
Incidence of AEs/SAEs
Time frame: From 1st dose to within 30 days of last dose
Any untoward medical occurrence associated with the use of study drug
MTD
Time frame: From 1st dose to within 30 days of last dose
To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached
RP2D
Time frame: From 1st dose to within 30 days of last dose
To determine recommended phase 2 dose of HMPL-760 in subjects
7 secondary outcomes
Objective Response Rate (ORR)
Time frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Duration of Response (DoR)
Time frame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
Clinical Benefit Rate (CBR)
Time frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Progression-free Survival (PFS)
Time frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Maximum Plasma Concentration [Cmax]
Time frame: From 1st dose to within 30 days of last dose
Chemokines
Time frame: From 1st dose to within 30 days of last dose
Phospho-BTK
Time frame: From 1st dose to within 30 days of last dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
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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.
Vijay Jayaprakash, MBBS, PHD study director
Hutchison Medipharma Limited
36 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMPL-760 in people with CLL/SLL and NHL, run by Hutchmed at 36 sites in 7 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 5 inclusion and 26 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: withdrawn, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Spain, France, Israel, Italy and 2 more countries. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Incidence of DLTs (time frame: Up to 28 days after first dose of study drug). The study lists 4 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 21 Feb 2023.