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Safety, Tolerability and Pharmacokinetics Study of KPG-818 in Hematological Malignancies Subjects

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04283097
Recruitment Status : Recruiting
First Posted : February 25, 2020
Last Update Posted : April 18, 2023
Sponsor:
Information provided by (Responsible Party):
Kangpu Biopharmaceuticals, Ltd.

Study Description
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Brief Summary:

This is a phase 1, multicenter, open-label, multiple-ascending dose study to evaluate the safety, pharmacokinetics and clinical activity of KPG-818 in subjects with hematological malignancies. Approximately 30 patients will be enrolled for dose escalation of 4 dose levels.

Indication: Hematological malignancies (multiple myeloma [MM], mantle cell lymphoma [MCL], diffuse large B-cell lymphoma [DLBCL], adult T-cell leukemia-lymphoma [ATL], and indolent non Hodgkin lymphomas such as follicular lymphoma [FL] and chronic lymphocytic leukemia [CLL]/small lymphocytic lymphoma [SLL]).


Condition or disease Intervention/treatment Phase
Hematological Malignancies Drug: KPG-818 Phase 1

Detailed Description:

This will be a dose escalation study in subjects with selected hematological malignancies. KPG-818 will be used in combination with dexamethasone in subjects with MM, and as monotherapy for other selected hematological malignancies. Each dose of KPG-818 will be administered orally until the completion of treatment cycles, or progressive disease (PD), unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met.

The highest dose level which may be tested is 5 mg KPG-818 and dose levels 2, 3, 4, and 5 mg and/or intermediate dosing or alternative dosing schedule may be explored. Each dose level (1-4) will be tested using the standard 3+3 design. DLT will be assessed during the DLT evaluation period (Cycle 1) and the treatment of study is divided into 6 cycles.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Dose escalation will use a standard 3+3 approach to establish a maximum tolerated dose (MTD), and the initial escalation dose level will be 2mg/day. Subjects may be enrolled at dose levels 2, 3, 4, and 5 mg and/or intermediate dosing or alternative dosing schedule
Masking: None (Open Label)
Masking Description: This is a open label Phase I study
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-label, Multiple-ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of KPG-818 in Subjects With Hematological Malignancies
Actual Study Start Date : September 13, 2021
Estimated Primary Completion Date : January 19, 2024
Estimated Study Completion Date : May 14, 2024
Arms and Interventions
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Arm Intervention/treatment
Experimental: Single arm
KPG-818 dose escalation
 Drug: KPG-818
The 4 planned dose level (cohorts) of KPG-818 will be explored: 2, 3, 4 and 5mg. Each dose of KPG-818 will be administered orally with approximately 240 ml of water daily, and used as a single agent in subjects with selected hematological malignancies (or in combination with dexamethasone weekly for MM), according to specific dosing schedule in each treatment cycle until disease progression, unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met. The treatment of study is divided into 6 cycles.
Other Name: KPG-818 capsules


Outcome Measures
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Primary Outcome Measures :
  1. Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Up to 6 months of treatment ]
    Number of Treatment-Emergent Adverse Events(TEAE), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and changes from baseline in laboratory parameters, vital signs, and ECG.

  2. Recommended Phase 2 Dose (RP2D) [ Time Frame: Up to 4 weeks of treatment ]
    Maximum tolerated dose defined as the highest dose level at which 33% or less subjects experience DLT as defined by the protocol.


Secondary Outcome Measures :
  1. PK profile of KPG-818: maximum observed plasma concentration (Cmax). [ Time Frame: Up to 4 weeks of treatment ]
  2. PK profile of KPG-818: time of the maximum observed plasma concentration (Tmax) [ Time Frame: Up to 4 weeks of treatment ]
  3. PK profile of KPG-818: area under the plasma concentration-time profile (AUC) from time zero to the last quantifiable concentration (AUC0-t). [ Time Frame: Up to 4 weeks of treatment ]
  4. PK profile of KPG-818: AUC from time zero extrapolated to infinity (AUC0-∞). [ Time Frame: Up to 4 weeks of treatment ]
  5. PK profile of KPG-818: AUC within a dosing interval (AUC0-τ). [ Time Frame: Up to 4 weeks of treatment ]
  6. PK profile of KPG-818: apparent total plasma clearance (CL/F). [ Time Frame: Up to 4 weeks of treatment ]
  7. PK profile of KPG-818: apparent total plasma clearance at steady-state (CLss/F). [ Time Frame: Up to 4 weeks of treatment ]
  8. PK profile of KPG-818: apparent volume of distribution (Vz/F) [ Time Frame: Up to 4 weeks of treatment ]
  9. PK profile of KPG-818: apparent volume of distribution at steady-state (Vss). [ Time Frame: Up to 4 weeks of treatment ]
  10. PK profile of KPG-818: apparent plasma terminal elimination. half-life (t1/2) [ Time Frame: Up to 4 weeks of treatment ]
  11. Assessment of clinical activity: objective response rate (ORR). [ Time Frame: Up to 6 months of treatment ]
    Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the 'Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma' (for ATL).

  12. Assessment of clinical activity: disease control rate (DCR). [ Time Frame: Up to 6 months of treatment ]
    Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the 'Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma' (for ATL).

  13. Assessment of clinical activity: time to response, duration of response. [ Time Frame: Up to 6 months of treatment ]
    Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the 'Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma' (for ATL).

  14. Assessment of clinical activity: progression-free survival. [ Time Frame: Up to 6 months of treatment ]
    Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the 'Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma' (for ATL).

  15. Assessment of clinical activity: event-free survival (EFS), and transplantation rate (TR). [ Time Frame: Up to 6 months of treatment ]
    Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the 'Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma' (for ATL).


Other Outcome Measures:
  1. Biomarkers of KPG-818 [ Time Frame: Up to 6 months of treatment ]
    Aiolos and Ikaros in peripheral blood mononuclear cell (PBMC)


Eligibility Criteria
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Information from the National Library of Medicine

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

Inclusion Criteria:

  1. ≥ 18 years of age
  2. Willing and able to provide written consent.
  3. Willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Hematocytological or pathological diagnosis of MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL, etc.
  5. Subjects who have relapsed from or are refractory to MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL.
  6. Have measurable or assessable disease.
  7. Meet the laboratory requirements:
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  9. Males and females of childbearing potential must agree to use at least two methods of contraception and continue until 3 months after the completion of study treatment.

Exclusion Criteria:

  1. Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Currently enrolled in another clinical study, except observational studies.
  3. Has known active central nervous system metastases and/or lymphomatous meningitis.
  4. Persisting toxicities related to prior anticancer treatment > Grade 1.
  5. Major surgery or significant traumatic injury within 6 weeks prior to Screening or planned major surgery during the study period.
  6. Received live attenuated vaccine within 4 weeks of first dose.
  7. Subjects with gastrointestinal disease that may significantly alter the absorption of the study drug.
  8. Subjects with a plasma cell leukemia.
  9. Subjects with prior history of malignancies, other than MM, lymphoma, or CLL/SLL, unless the subject has been free of the disease for ≥ 5 years.
  10. Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide.
  11. Has known or suspected hypersensitivity to the excipients contained in the formulation of investigational product (IP).
  12. Has been treated with an investigational agent (i.e., an agent not commercially available) within 28 days of initiating IP.
  13. Prior treatment of any inhibitors of PD-1 or PD-L1 within 3 months prior to initiating IP.

  14. Has any one of the following:

    • Clinically significant abnormal ECG finding at Screening.
    • Congestive heart failure.
    • Myocardial infarction within 12 months prior to initiating IP.
    • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris.
    • Peripheral neuropathy ≥ Grade 2.
    • Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John's Wort or related products within 2 weeks prior to dosing and during the course of study.
  15. Has current or prior use of immunosuppressive medication within 14 days prior initiating IP.
  16. Subject known to test positive for human immunodeficiency virus, active hepatitis B, or active hepatitis C.
  17. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.
  18. Subject is a female who is pregnant, nursing, or breastfeeding.
Contacts and Locations
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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): NCT04283097


Contacts
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Contact: Yao Wang, MD +19738738678 yao.wang@kangpugroup.com
Contact: Kai Wei, MD +8618201496205 kai.wei@kangpugroup.com

Locations
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United States, California
UC Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Aaron Rosenberg         
United States, Florida
BRCR Global - USA Recruiting
Plantation, Florida, United States, 33322
Contact: Harshad Amin         
United States, Kentucky
Norton Cancer Institute Completed
Louisville, Kentucky, United States, 40202
United States, Michigan
Henry Ford Health System - Hemophilia and Thrombosis Treatment Center Recruiting
Detroit, Michigan, United States, 48202-2689
Contact: Ahmad Mattour         
United States, New Jersey
Mohamad Medical Cherry Recruiting
Morristown, New Jersey, United States, 07960
Contact: Mohamad M Cherry         
United States, North Carolina
Duke University Health System - Duke Endoscopy - Duke Clinic 2H Recruiting
Durham, North Carolina, United States, 27710-4000
Contact: Christiana Costa Chase         
United States, Oregon
Providence Portland Medical Center Completed
Portland, Oregon, United States, 97213
United States, Pennsylvania
UPMC CancerCenter Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jing-Zhou Hou         
United States, Texas
Laguna Clinical Research Associates Recruiting
Laredo, Texas, United States, 78041
Contact: Eduardo Miranda         
United States, Wisconsin
Medical College of Wisconsin Active, not recruiting
Milwaukee, Wisconsin, United States, 53226-0509
Sponsors and Collaborators
Kangpu Biopharmaceuticals, Ltd.
Investigators
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Study Director: MD Kangpu Biopharmacuticals
More Information
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Responsible Party: Kangpu Biopharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT04283097    
Other Study ID Numbers: KPG-818-HEM-101
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: April 18, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases