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LymphomasPhase 1NCT03128164

A Study of HMPL-689 in Patients With Lymphomas Failed of Standard of Care or no Standard of Care Existed

A Phase 1 study testing HMPL-689 in people with Lymphomas, run by Hutchison Medipharma Limited at 3 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, open-label study of HMPL-689 administered orally to patients with lymphoma for whom failed of standard care or have no standard of care.This study consists of a dose escalation stage (Stage I) and a dose expansion stage (Stage II). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphomas
What is being tested?
HMPL-689
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
3 sitesChina
Study dates
8 Aug 2017to 2 Aug 2023
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

  • Signed Informed Consent Form (ICF)
  • Ability to comply with the protocol
  • Age ≥ 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically confirmed lymphoma
  • Relapsed or refractory disease after failed of standard of care or no standard of care existed according to local guideline, and need further systematic treatment in the opinion of the investigator
Show all 9Show fewer
  • At least 1 bi-dimensionally measurable nodal disease, defined as >1.5 cm (extra-nodal lesion>1.0 cm ) in its largest dimension by computerized tomography (CT) scan is required for patients with lymphoma other than CLL; lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by magnetic resonance image (MRI) instead
  • Expected survival of more than 24 weeks
  • Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use double barrier contraception, condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral or parenteral), Implanon®, injectable or other avoidance of pregnancy measures during the study and for 30 days after the last day of treatment. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from this criterion

Who cannot join

  • Patients with CNS(Central nervous system) involvement
  • Any of the following laboratory abnormalities:
  • Absolute neutrophil count < 1.5×109/L Hemoglobin <90 g/L Platelets< 100 ×109/L
  • Inadequate organ function, defined by the following:
  • Total bilirubin >1.5 x the upper limit of normal (ULN) with the following exception:
  • Patients with known Gilbert's disease who have serum total and direct bilirubin level ≤ 2.5 x the ULN and normal aspartate transaminase (AST) and alanine transaminase (ALT) may be enrolled
Show all 38Show fewer
  • AST or ALT >2.5 x the ULN with the following exception:
  • In the dose expansion stage:Patients with documented disease infiltration of the liver may have AST and ALT levels ≤ 5 x the ULN
  • Serum creatinine >1.5 x the ULN or estimated creatinine clearance (Ccr) (i.e., estimated Glomerular Filtration Rate, [eGFR[ according to the method of Cockcroft-Gault )< 60 mL/min
  • International normalized ratio (INR) >1.5 x the ULN or activated partial thromboplastin time (aPTT) >1.5 x the ULN or Prothrombin Time (PT) >1.5 x the ULN
  • Serum amylase or lipase >ULN at screening
  • Patients with presence of second primary malignant tumors within the last 5 years, with the exception of the following non-invasive malignancies after curative treatment:
  • Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for≥ 1 year prior to randomization
  • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
  • Prior treatment with any PI3K inhibitors and discontinued due to disease progression
  • Any anti-cancer therapy, including chemotherapy, radiotherapy within 3 weeks prior to initiation of study treatment
  • G-CSF/blood transfusion is prohibited 7 days before the screening hematology test
  • Any steroid therapy or approved targeted small molecule agents for anti-neoplastic intent within 7 days or approximately 5 half-lives, whichever is the longer, prior to initiation of study treatment
  • Any monoclonal antibody for anti-neoplastic intent within 6 weeks or 2 half-lives, whichever is the longer, prior to initiation of study treatment
  • Prior use of any anti-cancer vaccine
  • Prior administration of radioimmunotherapy within 3 months prior to initiation of study treatment
  • Prior use of any drug that is a strong inducer of CYP3A4, strong inhibitor of CYP3A4 within 2 weeks prior to initiation of study treatment (refer to Appendix 13)
  • Prior autologous transplant within 6 months prior to initiation of study treatment
  • Prior allogeneic stem cell transplant within 6 months prior to initiation of study treatment or with any evidence of active graft versus host disease or requirement for immunosuppressants within 21 days prior to initiation of study treatment
  • Clinically significant active infection (e.g., pneumonia)
  • Major surgical procedure within 4 weeks prior to initiation of study treatment
  • Treatment within a clinical study of an investigational agent or using an investigational device within 30 days prior to initiation of study treatment
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade 1, except for alopecia
  • Pregnant (positive pregnancy test) or lactating women
  • New York Heart Association (NYHA) Class II or greater congestive heart failure
  • Congenital long QT syndrome or QTc > 450 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 disease or ulcerative colitis)
  • History of drug-induced pneumonitis
  • 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

3 sites in 1 country.

China3 sites

  • Sun Yat-sen University cancer center

    Guangzhou, 510060

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

  • TongJi Medical College Huazhong University of Science& Technology

    Wuhan, Hubei, 430030

Other trials in China

About this study

Official title: A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Lymphomas Failed of Standard of Care or No Standard of Care Existed

This is a Phase 1, open-label study of HMPL-689 administered orally to patients with lymphoma for whom failed of standard care or have no standard of care.This study consists of a dose escalation stage (Stage I) and a dose expansion stage (Stage II).

Read the detailed description

Both Stage I and Stage II include the following periods: screening period, treatment period, safety follow-up period, and extended progression free survival (PFS) follow-up period, as defined in Dose Escalation Stage (Stage I).

Dose escalation will be performed according to a modified toxicity probability interval scheme-2 (mTPI-2).To further characterize safety and efficacy of HMPL-689 at RP2D, expansion stage of the study enrolled 144 patients with B cell lymphoma, including CLL/ SLL, FL, MZL, DLBCL, MCL and PTCL. Patients were treated with RP2D as starting dose.

Conditions
Lymphomas
Being tested
HMPL-689
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

    Two strengths of HMPL-689 capsules (2.5 mg and 10 mg) will be used for clinical studies. The drug products are capsules.

Study groups in NCT03128164
Study groupRoleWhat they receive
Six arm including in dose expansion stage by following:Experimental* Arm A: patients with MZL (subtype including nodal, extra-nodal and splenic) who received ≥ 1 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm B: patients with CLL/SLL who received ≥ 1 previous line of systematic treatment and at least one of which included purine-based regimen or CD20-directed regimen * Arm C: patients with FL (grade 1, 2, and 3a) who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm D: patients with MCL who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm E: patients with DLBCL (including GCB and non-GCB, Richter' transformation) who received ≥ 2 previous line of systematic treatment and at least one line included CD20-directed regimen * Arm F: patients with PTCL who received ≥ 2 previous line of systematic treatment
Receives: Drug: HMPL-689

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limited toxicities evaluated with NCI CTCAE v4.03

    Incidence of dose limited toxicities and associated dose of HMPL-689

    Measured: within 28 days after the first dose

  2. Objective response rate (ORR)

    Overall response rate (ORR) is defined as the proportion of patients who have a CR or PR

    Measured: Through study completion, 1 year after the last patient has enrolled in the study or all patients have discontinued the study, whichever comes sooner

Secondary outcomes (2)

  1. Maximum plasma concentration calculated with Blood samples

    Blood samples will be taken to measure the levels of study drug

    Measured: within 29 days after the first dose

  2. Time to reach maximum concentration calculated with Blood samples

    Blood samples will be taken to measure the levels of study drug

    Measured: within 29 days after the first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2017
  2. Study start8 Aug 2017
  3. Primary completion2 Aug 2023
  4. Study completion2 Aug 2023

Resources

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
Model description
This study consists of a dose escalation stage (Stage I) and a dose expansion stage (Stage II). Dose escalation will be performed according to a modified toxicity probability interval scheme-2 (mTPI-2). Expansion stage of the study enrolled 143 patients with B cell lymphoma, including CLL/SLL, FL, MZL, DLBCL, MCL and PTCL, Patients were treated with RP2D as starting dose.
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03128164
Sponsor's protocol ID
2016-689-GLOB1
Status last verified
Aug 2023
First submitted
30 Mar 2017
Last updated
23 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HMPL-689 in people with Lymphomas, run by Hutchison Medipharma Limited at 3 sites in China.

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 9 inclusion and 38 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: finished, as of the sponsor's last update on 23 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 limited toxicities evaluated with NCI CTCAE v4.03 (time frame: within 28 days after the first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03128164.

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 23 Aug 2023.

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