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

NCT04504708 | Terminated Phase 1 FDA Drug

• 1 other identifier: ZX-101A-101
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

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).

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Defining the recommended Phase 2 dose (RP2D) of ZX-101A.

  To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.

  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

  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

  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

  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

  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

  Days 1 and 2 of Cycle 1 (each cycle is 28 days)

• Objective response rate (ORR)

  Up to 2 years

Study Arms (5)

ZX-101A Dose Level 1

EXPERIMENTAL

Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle

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

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

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

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

Drug: ZX-101A

Interventions

ZX-101A DRUG

Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hangzhou Zenshine Pharmaceuticals Co., Ltd.: lead

Study Sites (6)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

ACRC/Arizona Clinical Research Center, Inc.

Tucson, Arizona, 85715, United States

Location

Innovative Clinical Research Institute

Long Beach, California, 90804, United States

Location

New Jersey Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

University of Toledo Precision Oncology Research

Toledo, Ohio, 43614, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Xiaolin Qin, PhD

  Zenshine Pharmaceutical, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2020
• First Posted: August 7, 2020
• Study Start: February 17, 2021
• Primary Completion: July 8, 2022
• Study Completion: July 8, 2022
• Last Updated: October 21, 2022

Record last verified: 2022-10

Locations

US (6)