Clinical Trials /

Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies

NCT04504708

Description:

ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies [Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other NHL subtypes).

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
  • Official Title: A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: ZX-101A-101
  • NCT ID: NCT04504708

Conditions

  • Non-hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
ZX-101AZX-101A Dose Level 1

Purpose

ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies [Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other NHL subtypes).

Detailed Description

      The ZX-101A-101 study will consist of 2 parts:

        -  Part 1: ZX-101A Dose Escalation

        -  Part 2: ZX-101A Dose Expansion

      The Part 1 (dose escalation) of the study is designed to determine the safety and
      tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose
      expansion) of the study is designed to further investigate the safety, tolerability,
      pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally
      once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).

      Results of clinical findings in patients in the dose-escalation portion of the study will be
      reviewed to identify conditions (or genetic characteristics) most likely to respond to
      ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the
      dose-expansion part of the study.

      Male or female patients who are 18 years of age or older with relapsed/resistant or
      refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be
      included in the study provided that all inclusion and exclusion criteria are satisfied.

      Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1)
      relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic
      Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL),
      and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other
      types of NHL may be included.
    

Trial Arms

NameTypeDescriptionInterventions
ZX-101A Dose Level 1ExperimentalStarting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
  • ZX-101A
ZX-101A Dose Level 2Experimental2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
  • ZX-101A
ZX-101A Dose Level 3Experimental3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
  • ZX-101A
ZX-101A Dose Level 4Experimental4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
  • ZX-101A
ZX-101A Dose Level 5Experimental5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
  • ZX-101A

Eligibility Criteria

        Inclusion Criteria:

          -  Males and females who are ≥ 18 years old

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

          -  Failed at least 2 prior systemic standard therapies.

          -  Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes.

          -  Documented active disease that is relapsed/resistant or refractory requiring treatment
             after established therapy shown to have clinical benefit.

          -  Acceptable bone marrow, kidney, and liver function.

          -  No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment.

          -  Ability to swallow and retain oral medications (see exclusion criteria #20 below).

          -  Negative serum pregnancy test in women of childbearing potential at Screening.

          -  Women of childbearing potential and men who partner with a woman of childbearing
             potential must agree to use effective contraceptive methods.

          -  Men must agree to no sperm donations during the study and for 3 months after the last
             dose of ZX-101A.

          -  Understands the requirements of the study (e.g. periodic imaging studies, periodic
             blood sampling, bone marrow studies), is willing to comply with all study procedures
             and signed the Institutional Review Board (IRB)-approved informed consent.

        Exclusion Criteria:

          -  Received investigational study drug within 28 days (or 5 half-lives, whichever is
             longer).

          -  Concurrent participation in another therapeutic treatment trial.

          -  Received approved anti-cancer drugs within 21 days (42 days for nitrosoureas) or 5
             half-lives, whichever is longer.

          -  Ongoing immunosuppression for chronic conditions.

          -  Known active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.

          -  Any concurrent uncontrolled illness.

          -  Has not recovered from adverse events from prior anti-cancer treatment (with exception
             of alopecia).

          -  Pregnant or breast-feeding or planning to conceive or father children within the
             projected duration of the study.

          -  Major surgery within 4 weeks prior to first dose of study treatment.

          -  Radiation treatment within 2 weeks prior to first dose of study treatment.

          -  Gastrointestinal dysfunction, including motility or malabsorption syndromes or
             inflammatory bowel disease which could limit absorption of study drug.

          -  Active or prior pneumonitis or interstitial lung disease.

        Other inclusion and exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
Time Frame:From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.
Safety Issue:
Description:To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.

Secondary Outcome Measures

Measure:Peak Plasma Concentration of ZX-101A
Time Frame:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Safety Issue:
Description:To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A
Measure:Area under the plasma concentration of ZX-101A
Time Frame:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Safety Issue:
Description:To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A
Measure:Half-life of ZX-101A
Time Frame:Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Safety Issue:
Description:To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A
Measure:Phospho-AKT (p-AKT) levels in whole blood
Time Frame:Days 1 and 2 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.
Measure:Objective response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Measure:Duration of response (DoR)
Time Frame:Up to 2 years
Safety Issue:
Description:To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause
Measure:Progression free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hangzhou Zenshine Pharmaceuticals Co., Ltd.

Last Updated

January 12, 2021