Non-hodgkin LymphomaPhase 1/2NCT04504708
Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
A Phase 1/2 study testing ZX-101A in people with Non-hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by Hangzhou Zenshine Pharmaceuticals Co., Ltd. at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- ZX-101A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 6 sitesUnited States
- Study dates
- 17 Feb 2021to 8 Jul 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
New Jersey Center for Cancer Research
Brick, New Jersey, 08724
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Innovative Clinical Research Institute
Long Beach, California, 90804
Seattle Cancer Care Alliance
Seattle, Washington, 98109
University of Toledo Precision Oncology Research
Toledo, Ohio, 43614
ACRC/Arizona Clinical Research Center, Inc.
Tucson, Arizona, 85715
About this study
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
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).
Read the 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.
- Being tested
- ZX-101A
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZX-101ADrug
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| ZX-101A Dose Level 1 | Experimental | Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle Receives: Drug: ZX-101A |
| ZX-101A Dose Level 2 | Experimental | 2-times the SD of ZX-101A administered orally once daily in a 28-day cycle Receives: Drug: ZX-101A |
| ZX-101A Dose Level 3 | Experimental | 3-times the SD of ZX-101A administered orally once daily in a 28-day cycle Receives: Drug: ZX-101A |
| ZX-101A Dose Level 4 | Experimental | 4-times the SD of ZX-101A administered orally once daily in a 28-day cycle Receives: Drug: ZX-101A |
| ZX-101A Dose Level 5 | Experimental | 5-times the SD of ZX-101A administered orally once daily in a 28-day cycle Receives: Drug: ZX-101A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
Measured: 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 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
Measured: 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 outcomes (8)
Peak Plasma Concentration of ZX-101A
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A
Measured: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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
Measured: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Half-life of ZX-101A
To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A
Measured: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
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.
Measured: Days 1 and 2 of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR)
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Measured: Up to 2 years
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
Measured: Up to 2 years
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
Measured: Up to 2 years
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
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2020
- Study start17 Feb 2021
- Primary completion8 Jul 2022
- Study completion8 Jul 2022
Why it stopped: Study terminated early due to business decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hangzhou Zenshine Pharmaceuticals Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xiaolin Qin, PhD, Study director, Zenshine Pharmaceutical, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04504708
- Sponsor's protocol ID
- ZX-101A-101
- Status last verified
- Oct 2022
- First submitted
- 25 Jul 2020
- Last updated
- 21 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04504708
- Acronym / sponsor ID
- ZX-101A-101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early due to business decision.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Hangzhou Zenshine Pharmaceuticals Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 17 Feb 2021 (actual)
- Primary completion
- 8 Jul 2022 (actual)
- Study completion
- 8 Jul 2022 (actual)
- First posted
- 7 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| ZX-101A Dose Level 1 | Experimental | Drug: ZX-101AStarting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle |
| ZX-101A Dose Level 2 | Experimental | Drug: ZX-101A2-times the SD of ZX-101A administered orally once daily in a 28-day cycle |
| ZX-101A Dose Level 3 | Experimental | Drug: ZX-101A3-times the SD of ZX-101A administered orally once daily in a 28-day cycle |
| ZX-101A Dose Level 4 | Experimental | Drug: ZX-101A4-times the SD of ZX-101A administered orally once daily in a 28-day cycle |
| ZX-101A Dose Level 5 | Experimental | Drug: ZX-101A5-times the SD of ZX-101A administered orally once daily in a 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZX-101AOnce daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle | Drug | 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 |
Primary outcome
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.
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
8 secondary outcomes
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
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
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
Phospho-AKT (p-AKT) levels in whole blood
Time frame: Days 1 and 2 of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR)
Time frame: Up to 2 years
Duration of response (DoR)
Time frame: Up to 2 years
Progression free survival (PFS)
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Results and safety
The study was stopped early (reason given: Study terminated early due to business decision.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaolin Qin, PhD study director
Zenshine Pharmaceutical, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZX-101A in people with Non-hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by Hangzhou Zenshine Pharmaceuticals Co., Ltd. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated early due to business decision.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2022.