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

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ClinicalTrials.gov Identifier: NCT04504708
Recruitment Status : Recruiting
First Posted : August 7, 2020
Last Update Posted : August 30, 2021
Sponsor:
Information provided by (Responsible Party):
Hangzhou Zenshine Pharmaceuticals Co., Ltd.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Non-hodgkin Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: ZX-101A Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 17, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ZX-101A Dose Level 1
Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
Drug: ZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

Experimental: ZX-101A Dose Level 2
2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Drug: ZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

Experimental: ZX-101A Dose Level 3
3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Drug: ZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

Experimental: ZX-101A Dose Level 4
4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Drug: ZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

Experimental: ZX-101A Dose Level 5
5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Drug: ZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle




Primary Outcome Measures :
  1. 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. ]
    To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.

  2. Safety and tolerability of ZX-101A [ Time Frame: From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days. ]
    To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2


Secondary Outcome Measures :
  1. 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 ]
    To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A

  2. 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 ]
    To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A

  3. 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 ]
    To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A

  4. Phospho-AKT (p-AKT) levels in whole blood [ Time Frame: Days 1 and 2 of Cycle 1 (each cycle is 28 days) ]
    To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.

  5. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    To evaluate the objective response rate (ORR) as determined by the specific disease response criteria

  6. Duration of response (DoR) [ Time Frame: Up to 2 years ]
    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

  7. Progression free survival (PFS) [ Time Frame: Up to 2 years ]
    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

  8. Overall survival (OS) [ Time Frame: Up to 2 years ]
    To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.


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): NCT04504708


Contacts
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Contact: Xiaolin Qin, PhD +1-650-799-2796 xiaoli.qin@zenshine-pharm.com
Contact: Edgar Bautista +1-310-867-9063 Edgar@zenshine-pharma.com

Locations
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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Aileen Go, MD         
Principal Investigator: Aileen Go, MD         
ACRC/Arizona Clinical Research Center, Inc. Recruiting
Tucson, Arizona, United States, 85715
Contact: Manuel R Modiano, MD         
United States, California
Innovative Clinical Research Institute Recruiting
Long Beach, California, United States, 90804
Contact: John Khoury, MD         
United States, New Jersey
New Jersey Center for Cancer Research Recruiting
Brick, New Jersey, United States, 08724
Contact: Apurv Agrawal, MD         
United States, Ohio
University of Toledo Precision Oncology Research Recruiting
Toledo, Ohio, United States, 43614
Contact: Roland Skeel, MD         
Sponsors and Collaborators
Hangzhou Zenshine Pharmaceuticals Co., Ltd.
Investigators
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Study Director: Xiaolin Qin, PhD Zenshine Pharmaceutical, Inc.
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Responsible Party: Hangzhou Zenshine Pharmaceuticals Co., Ltd.
ClinicalTrials.gov Identifier: NCT04504708    
Other Study ID Numbers: ZX-101A-101
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: August 2021

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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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Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Neoplasms by Site
Hematologic Diseases