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

April 14, 2023 updated by: Kangpu Biopharmaceuticals, Ltd.

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

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]).

Study Overview

Status

Recruiting

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis Comprehensive Cancer Center
        • Contact:
          • Aaron Rosenberg
    • Florida
      • Plantation, Florida, United States, 33322
        • Recruiting
        • BRCR Global - USA
        • Contact:
          • Harshad Amin
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Completed
        • Norton Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202-2689
        • Recruiting
        • Henry Ford Health System - Hemophilia and Thrombosis Treatment Center
        • Contact:
          • Ahmad Mattour
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Recruiting
        • Mohamad Medical Cherry
        • Contact:
          • Mohamad M Cherry
    • North Carolina
      • Durham, North Carolina, United States, 27710-4000
        • Recruiting
        • Duke University Health System - Duke Endoscopy - Duke Clinic 2H
        • Contact:
          • Christiana Costa Chase
    • Oregon
      • Portland, Oregon, United States, 97213
        • Completed
        • Providence Portland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • Upmc Cancercenter
        • Contact:
          • Jing-Zhou Hou
    • Texas
      • Laredo, Texas, United States, 78041
        • Recruiting
        • Laguna Clinical Research Associates
        • Contact:
          • Eduardo Miranda
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226-0509
        • Active, not recruiting
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single arm
KPG-818 dose escalation
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 Names:
  • KPG-818 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months of treatment
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.
Up to 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PK profile of KPG-818: maximum observed plasma concentration (Cmax).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: time of the maximum observed plasma concentration (Tmax)
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
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
Up to 4 weeks of treatment
PK profile of KPG-818: AUC from time zero extrapolated to infinity (AUC0-∞).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: AUC within a dosing interval (AUC0-τ).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: apparent total plasma clearance (CL/F).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: apparent total plasma clearance at steady-state (CLss/F).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: apparent volume of distribution (Vz/F)
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: apparent volume of distribution at steady-state (Vss).
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
PK profile of KPG-818: apparent plasma terminal elimination. half-life (t1/2)
Time Frame: Up to 4 weeks of treatment
Up to 4 weeks of treatment
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).
Up to 6 months of treatment
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).
Up to 6 months of treatment
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).
Up to 6 months of treatment
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).
Up to 6 months of treatment
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).
Up to 6 months of treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarkers of KPG-818
Time Frame: Up to 6 months of treatment
Aiolos and Ikaros in peripheral blood mononuclear cell (PBMC)
Up to 6 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: MD, Kangpu Biopharmacuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 13, 2021

Primary Completion (Anticipated)

January 19, 2024

Study Completion (Anticipated)

May 14, 2024

Study Registration Dates

First Submitted

February 21, 2020

First Submitted That Met QC Criteria

February 21, 2020

First Posted (Actual)

February 25, 2020

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 14, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • KPG-818-HEM-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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