Back to resultsDose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
Primary Purpose
Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ZX-101A
Sponsored by
About this trial
This is an interventional treatment trial for Non-hodgkin Lymphoma
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.
Sites / Locations
- Banner MD Anderson Cancer Center
- ACRC/Arizona Clinical Research Center, Inc.
- Innovative Clinical Research Institute
- New Jersey Center for Cancer Research
- University of Toledo Precision Oncology Research
- Seattle Cancer Care Alliance
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
ZX-101A Dose Level 1
ZX-101A Dose Level 2
ZX-101A Dose Level 3
ZX-101A Dose Level 4
ZX-101A Dose Level 5
Arm Description
Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Outcomes
Primary Outcome Measures
Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
Safety and tolerability of ZX-101A
To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2
Secondary Outcome Measures
Peak Plasma Concentration of ZX-101A
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A
Area under the plasma concentration of ZX-101A
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A
Half-life of ZX-101A
To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A
Phospho-AKT (p-AKT) levels in whole blood
To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.
Objective response rate (ORR)
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Duration of response (DoR)
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
Progression free survival (PFS)
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
Overall survival (OS)
To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause
Full Information
NCT ID
NCT04504708
First Posted
July 25, 2020
Last Updated
October 19, 2022
Sponsor
Hangzhou Zenshine Pharmaceuticals Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04504708
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
Study terminated early due to business decision.
Study Start Date
February 17, 2021 (Actual)
Primary Completion Date
July 8, 2022 (Actual)
Study Completion Date
July 8, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hangzhou Zenshine Pharmaceuticals Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ZX-101A Dose Level 1
Arm Type
Experimental
Arm Description
Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
Arm Title
ZX-101A Dose Level 2
Arm Type
Experimental
Arm Description
2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Arm Title
ZX-101A Dose Level 3
Arm Type
Experimental
Arm Description
3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Arm Title
ZX-101A Dose Level 4
Arm Type
Experimental
Arm Description
4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Arm Title
ZX-101A Dose Level 5
Arm Type
Experimental
Arm Description
5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
Intervention Type
Drug
Intervention Name(s)
ZX-101A
Intervention Description
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Primary Outcome Measure Information:
Title
Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
Description
To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
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.
Title
Safety and tolerability of ZX-101A
Description
To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2
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.
Secondary Outcome Measure Information:
Title
Peak Plasma Concentration of ZX-101A
Description
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses 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
Title
Area under the plasma concentration of ZX-101A
Description
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses 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
Title
Half-life of ZX-101A
Description
To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses 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
Title
Phospho-AKT (p-AKT) levels in whole blood
Description
To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.
Time Frame
Days 1 and 2 of Cycle 1 (each cycle is 28 days)
Title
Objective response rate (ORR)
Description
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Time Frame
Up to 2 years
Title
Duration of response (DoR)
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
Time Frame
Up to 2 years
Title
Progression free survival (PFS)
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
Time Frame
Up to 2 years
Title
Overall survival (OS)
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
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaolin Qin, PhD
Organizational Affiliation
Zenshine Pharmaceutical, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
ACRC/Arizona Clinical Research Center, Inc.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Long Beach
State/Province
California
ZIP/Postal Code
90804
Country
United States
Facility Name
New Jersey Center for Cancer Research
City
Brick
State/Province
New Jersey
ZIP/Postal Code
08724
Country
United States
Facility Name
University of Toledo Precision Oncology Research
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
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