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A First-in-Human Study of PRL3-ZUMAB

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03191682
Recruitment Status : Unknown
Verified February 2019 by National University Hospital, Singapore.
Recruitment status was:  Recruiting
First Posted : June 19, 2017
Last Update Posted : September 3, 2019
Sponsor:
Collaborator:
INTRA-IMMUSG PRIVATE LIMITED
Information provided by (Responsible Party):
National University Hospital, Singapore

Brief Summary:
This study is carried out to test the safety of a study drug called PRL3-ZUMAB. PRL3-ZUMAB is an investigational drug that has not yet been approved by the Food and Drug Administration (FDA) or any other regulatory authorities for commercial purposes. This is the first study in which PRL3-ZUMAB will be given to humans. The study drug has been tested in animals and was found to be well-tolerated with minimal side effects. This research study will test different doses of the drug to see which dose is safest in people.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: PRL3-ZUMAB Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, First-in-Human Study of PRL3-ZUMAB In Advanced, Solid Tumors and Haematologic Malignancies
Actual Study Start Date : February 20, 2017
Estimated Primary Completion Date : February 20, 2020
Estimated Study Completion Date : February 20, 2020

Arm Intervention/treatment
Experimental: PRL3-ZUMAB
The starting dose will be 0.3 mg/kg, administered Q2 weekly, with the subsequent dose levels being 0.9 mg/kg, 3.0 mg/kg, and 6.0 mg/kg, all administered on a Q2 weekly basis until disease progression
Drug: PRL3-ZUMAB
The starting dose will be 0.3 mg/kg, administered Q2 weekly, with the subsequent dose levels being 0.9 mg/kg, 3.0 mg/kg, and 6.0 mg/kg, all administered on a Q2 weekly basis until disease progression. The investigator will monitor each subject for the occurrence of AEs. In event of infusion-related adverse events, the Investigator, in consultation with the PI, may increase the duration of the infusion over a period of up to 24 hours at their discretion. Dosing will continue in a standard 3+3 design for dose escalation.




Primary Outcome Measures :
  1. Incidence of Grade 3 or 4 drug related adverse events and clinical lab abnormalities defined as Dose Limiting Toxicities (DLTs) using NCI CTCAE v 4.03 [ Time Frame: During cycle 1 (28 days) of treatment ]
  2. Maximum tolerated dose of PRL3-zumab, defined as the highest dose level at which < 33% of 6 patients experience a dose-limiting toxicity graded according to Common Terminology Criteria for Adverse Events version 4 (Phase I) [ Time Frame: 28 days ]
  3. Recommended Phase 2 Dose (RP2D) of PRL3-zumab defined as the most appropriate dose to maximize a favorable risk/benefit reward for the participant population [ Time Frame: After completion of all Cycle 1 (28 days) of treatment for participant enrolled in part 1 ]

Secondary Outcome Measures :
  1. Total Active Pharmaceutical Ingredient (API) levels in plasma [ Time Frame: The pharmacokinetics profile will be assessed by blood collection during Cycle 1 (28 days) of treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent. Written informed consent must be obtained prior to performing any study-related procedures.
  2. Histopathological- or cytological- documented, measurable or non-measurable, locally advanced unresectable primary or metastatic solid tumor unresponsive to standard therapy or for which there is no standard therapy available.
  3. Progressive disease (PD) during or following the last treatment regimen as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1 guidelines)
  4. Haematologic malignancies study population for expansion cohort:

    • Newly diagnosed early AML (age>65 years) who are unfit for the intensive chemotherapy and declined hypomethylating agent
    • Elderly AML who failed first line of treatment including hypomethylating agent
    • Relapsed or refractory AML who failed at least 1 line of salvage chemotherapy and are deemed unfit for further intensive chemotherapy
    • Relapsed or refractory multiple myeloma who failed at least 3 lines of prior therapy and with measurable disease either by serum M-protein, involved immunoglobulin type or serum free light chain.
  5. Life expectancy >3 months
  6. Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of <= 2 at study entry
  7. Age ≥ 21 years
  8. Pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) ≥ 50%
  9. Recovery to Grade ≤ 1 by the Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE v 4.03), from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for cancer, with the exception of alopecia or peripheral neuropathy (the latter of which must have resolved to Grade ≤ 2).
  10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at study entry. Subjects not considered WOCBP are those without menses for 24 consecutive months, and those who have undergone hysterectomy and/or bilateral salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study.
  11. Preserved organ function as defined below. All parameters must be evaluated within 7 days prior to the first dose of PRL3-ZUMAB:

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN), or ≤ 5.0 X ULN in subjects with metastatic liver disease
    • Hemoglobin ≥ 9 g/dL
    • Total bilirubin ≤ 1.5 × ULN
    • Creatinine ≤ 1.5 × ULN
    • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (only applicable to non-AML subject)
    • Platelets ≥ 100 × 109/L (only applicable to non-AML subject)

Exclusion Criteria:

  1. Prior anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, monoclonal antibodies, targeted therapy or investigational agents within 4 weeks (6 weeks for mitomycin C and nitrosoureas) prior to the first dose of PRL3-ZUMAB
  2. Known symptomatic brain metastases. Subjects with treated brain metastasis (radiotherapy and/or surgery) will be eligible if they:

    • Have completed treatment for their brain metastasis > 4 weeks prior to scheduled study treatment start date;
    • Are neurologically stable;
    • Are not receiving corticosteroids or corticosteroids in doses no greater than physiological replacement (e.g., dexamethasone < 1.5 mg/day); and
    • Have a screening/baseline MRI scan of the brain that specifically verifies no evidence of CNS hemorrhage and no active gadolinium enhancing lesions.
  3. Isolated CNS disease in AML cohort
  4. Acute promyelocytic leukemia or AML M3
  5. Non-secretary myeloma
  6. Primary brain / CNS malignancy (e.g., gliomas, lymphomas)
  7. Leptomeningeal disease
  8. Pregnancy (confirmed by beta -human chorionicgonadotrophin [β-HCG] or lactating
  9. Significant uncontrolled intercurrent illness including, but not limited to:

    • ongoing or active infection requiring parenteral antibiotics; clinically significant cardiac disease [(class II, III, or IV of the New York Heart Association classification (NYHA)];
    • unstable angina pectoris, myocardial infarction within 6 months or is post angioplasty or stenting within 6 months;
    • uncontrolled hypertension (i.e., systolic blood pressure (BP) > 150 mm Hg, diastolic BP > 90 mm Hg), found on two consecutive measurements separated by a 1-week period;
    • clinically significant cardiac arrhythmia; or
    • uncontrolled diabetes.
  10. Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
  11. Known active hepatitis B or C or other active (nonmalignant) liver disease. Patients with hepatitis B surface antigen positive serology may participate if HBV DNA copy number is <100 copies/mL.
  12. History of previously treated neurologic or other neurodegenerative diseases/disorders, or psychiatric illness, disability, or social situation that would compromise the subject's safety, ability to provide consent, or limit his/her compliance with study requirements
  13. Prior hypersensitivity reaction to monoclonal antibodies or other therapeutic proteins, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-HT3 antagonists, or corticosteroids.
  14. History of another primary cancer, with the exception of:

    • curatively resected nonmelanomatous skin cancer,
    • curatively treated cervical carcinoma in-situ,
    • prostate cancer treated with leuteinizing hormone-releasing hormone (LH-RH) agonists/pure antagonists for at least 2 months, or
    • other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years.
  15. Require treatment with prohibited concomitant medications
  16. Prior stem cell or bone marrow transplant
  17. Vaccinated within 8 weeks from prior to the first administration of PRL3-ZUMAB

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): NCT03191682


Contacts
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Contact: Cheng Ean Chee (65) 6772 4621 cheng_ean_chee@nuhs.edu.sg

Locations
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Singapore
National University Hospital Recruiting
Singapore, Singapore, 119.074
Contact: Chin Hin Ng    (65) 6779 5555    chin_hin_ng@nuhs.edu.sg   
Sponsors and Collaborators
National University Hospital, Singapore
INTRA-IMMUSG PRIVATE LIMITED
Investigators
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Principal Investigator: Cheng Ean Chee National University Hospital, Singapore
Publications:
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Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03191682    
Other Study ID Numbers: MC03/06/16
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: September 3, 2019
Last Verified: February 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