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

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ClinicalTrials.gov Identifier: NCT03128164
Recruitment Status : Recruiting
First Posted : April 25, 2017
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief 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 will consist of a dose escalation stage (Stage I) and a dose expansion stage (Stage II).

Condition or disease Intervention/treatment Phase
Lymphomas Drug: HMPL-689 Phase 1

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 will enroll 56 patients with B cell lymphoma, including CLL, SLL, FL, MZL, WM, DLBCL, burkitt lymphoma and MCL. Patients will be treated with RP2D as starting dose.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 83 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This study will consist 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 will enroll 56 patients with B cell lymphoma, including CLL, SLL, FL, MZL, WM, DLBCL, burkitt lymphoma and MCL.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 8, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: HMPL-689
HMPL-689, oral, BID, doses should be taken at ~12-hour intervals (eg, at ~8 AM and at ~8 PM)
Drug: HMPL-689
Two strengths of HMPL-689 capsules (2.5 mg and 10 mg) will be used for clinical studies. The drug products are capsules.




Primary Outcome Measures :
  1. Dose limited toxicities evaluated with NCI CTCAE v4.03 [ Time Frame: within 28 days after the first dose ]
    Incidence of dose limited toxicities and associated dose of HMPL-689


Secondary Outcome Measures :
  1. Maximum plasma concentration calculated with Blood samples [ Time Frame: within 29 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug

  2. Time to reach maximum concentration calculated with Blood samples [ Time Frame: within 29 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug


Other Outcome Measures:
  1. Adverse events evaluated by NCI CTCAE v4.03 [ Time Frame: from the first dose to within 30 days after the last dose ]
    Incidence of adverse events and associated dose of HMPL-689

  2. Objective response rate [ Time Frame: within 30 days after the last dose ]
    the proportion of subjects who have a Complete Response or Partial Response



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent Form (ICF)
  2. Ability to comply with the protocol
  3. Age 18 and 75 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Histologically confirmed lymphoma
  6. Failed of standard of care or no standard of care existed according to local guideline

    a. At least 1 bi-dimensionally measurable nodal disease, defined as >1.5 cm in its largest dimension by computerized tomography (CT) scan is required for patients with lymphoma other than CLL

  7. In the dose expansion stage, patient recruitment will be restricted to the following lymphoma subtypes:

    • B cell lymphoma, including CLL, SLL, FL, MZL,WM, DLBCL, burkitt lymphoma and MCL

  8. Expected survival of more than 24 weeks
  9. Male or female patients 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 90 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

Exclusion Criteria:

  1. Patients with CNS(Central nervous system) involvement
  2. Any of the following laboratory abnormalities:

    • Absolute neutrophil count 1.5×109/L
    • Hemoglobin< 80 g/L
    • Platelets < 75 ×109/L
  3. 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

    • 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
  4. 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
  5. 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
  6. 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)
  7. Prior treatment with any PI3Kδ inhibitors

    - In stage II, patients discontinued PI3Kδ inhibitors for reasons other than disease progression are eligible

  8. Any anti-cancer therapy, including chemotherapy, radiotherapy within 3 weeks prior to initiation of study treatment
  9. G-CSF/blood transfusion is prohibited 7 days before the screening hematology test
  10. 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
  11. Any monoclonal antibody for anti-neoplastic intent within 6 weeks or 2 half-lives, whichever is the longer, prior to initiation of study treatment
  12. Prior use of any anti-cancer vaccine
  13. Prior administration of radioimmunotherapy within 3 months prior to initiation of study treatment
  14. 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)
  15. Prior autologous transplant within 6 months prior to initiation of study treatment
  16. 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
  17. Clinically significant active infection (e.g., pneumonia)
  18. Major surgical procedure within 4 weeks prior to initiation of study treatment
  19. Treatment within a clinical study of an investigational agent or using an investigational device within 30 days prior to initiation of study treatment
  20. Adverse events from prior anti-cancer therapy that have not resolved to Grade 1, except for alopecia
  21. Pregnant (positive pregnancy test) or lactating women
  22. New York Heart Association (NYHA) Class II or greater congestive heart failure
  23. Congenital long QT syndrome or QTc > 450 msec
  24. Currently use medication known to cause QT prolongation or torsades de pointes
  25. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment
  26. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment
  27. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
  28. History of inflammatory bowel disease (e.g., Crohn disease or ulcerative colitis)
  29. History of drug-induced pneumonitis
  30. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03128164


Locations
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China, Hubei
TongJi Medical College Huazhong University of Science& Technology Recruiting
Wuhan, Hubei, China, 430030
Contact: JianFeng Zhou    027-83662688    jfzhou@tjh.tjmu.edc.cn   
Principal Investigator: JianFeng Zhou         
China
Sun Yat-sen University cancer center Recruiting
Guangzhou, China, 510060
Contact: zhiming Li    020-87343392    lzmsysu@163.com   
Fudan University Shanghai Cancer Hospital Recruiting
Shanghai, China, 200032
Contact: Junning Cao    021-64175590    cao_junning@126.com   
Principal Investigator: Junning Cao         
Sponsors and Collaborators
Hutchison Medipharma Limited

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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT03128164     History of Changes
Other Study ID Numbers: 2016-689-GLOB1
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases