AL Amyloidosis, Amyloidosis
Conditions
Keywords
Amyloidosis, AL Amyloidosis, RRAL, BCL2 Inhibitor, t(11;14), ZN-d5, Light Chain Amyloidosis, Light chain (AL) Amyloidosis
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.
Interventions
DRUGZN-d5
ZN-d5 will be administered orally
Sponsors
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid. 2. Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy; 3. 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; 4. Measurable disease defined by serum differential free light chain; 5. Assessment of t(11,14) status by FISH; 6. Eastern Cooperative Oncology Group performance status ≤2 ; 7. History of organ involvement 8. Adequate bone marrow function prior to first administration of study drug; 9. Adequate organ function; Key
Exclusion criteria
1. Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis; 2. Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria; 3. Mayo 2012 Stage IV disease; 4. Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias. 5. Prior treatment with other BCL-2 inhibitors;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 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 |
| Dose limiting toxicities | 18 Months | Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Finding max concentration (Cmax) of ZN-d5 | 48 months | Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels. |
| PK Parameter: Finding half-life of ZN-d5 | 48 months | The time takes for half the drug concentration of ZN-d5 to be eliminated (Half-life) from the plasma that was collected from subjects at different dose levels |
| PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5 | 48 months | The total exposure of ZN-d5 over time (AUC) from the plasma collected by the subject at different dose levels. |
| Assess the hematologic response to ZN-d5 | 48 months | The number of Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR), Progressive Disease (PD) using the AL Amyloidosis Hematologic Response Criteria. |
| Duration and time to hematologic response to ZN-d5 | 48 months | The rate of, duration of, and time to CR, modified Complete Response (mCR), CR+VGPR, and mCR+VGPR |
| PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5 | 48 months | The duration (in hours) it takes for ZN-d5 to reach the maximum concentration (or Cmax) collected in the plasma from subjects at different dose levels. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess potential biomarker of ZN-d5 | 48 months | The number of peripheral B-Cells from blood tests |
Countries
Australia, Cyprus, Greece, Israel, Italy, Spain, United States
Outcome results
None listed