A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 135
- Locations
- 21
- Primary Endpoint
- Dose limiting toxicities
Study Overview
Brief Summary
This is a single arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis.
Detailed Description
A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis. The first part of the study is phase 1 dose-escalation and the second part will be phase 2.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
- •Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy;
- •At least 3 months from hematopoietic stem cell transplantation or the shorter of 60 days or 5 half-lives for biologics, small molecules, or investigational drugs prior to starting treatment;
- •Measurable disease defined by serum differential free light chain;
- •Assessment of t(11,14) status by FISH;
- •Eastern Cooperative Oncology Group performance status ≤2 ;
- •History of organ involvement
- •Adequate bone marrow function prior to first administration of study drug;
- •Adequate organ function;
Exclusion Criteria
- •Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis;
- •Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria;
- •Mayo 2012 Stage IV disease;
- •Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias.
- •Prior treatment with other BCL-2 inhibitors;
Arms & Interventions
Treatment Arm
Subjects will receive ZN-d5 orally (PO), once (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: ZN-d5 (Drug)
Outcomes
Primary Outcomes
Dose limiting toxicities
Time Frame: 18 Months
Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects
Safety and Tolerability
Time Frame: 18 Months
Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Secondary Outcomes
- PK Parameter: Finding max concentration (Cmax) of ZN-d5(48 months)
- PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5(48 months)
- Duration and time to hematologic response to ZN-d5(48 months)
- PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5(48 months)
- PK Parameter: Finding half-life of ZN-d5(48 months)
- Assess the hematologic response to ZN-d5(48 months)