Clinical trial NCT05199337: Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
Official title: A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Amyloidosis
AL Amyloidosis
Keywords: Amyloidosis
AL Amyloidosis
RRAL
BCL2 Inhibitor
t(11;14)
ZN-d5
Light Chain Amyloidosis
Light chain (AL) Amyloidosis
Lead sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-20
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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;

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 18 Months
measure: Dose limiting toxicities
timeFrame: 18 Months
Secondary outcomes:
measure: PK Parameter: Finding max concentration (Cmax) of ZN-d5
timeFrame: 48 months
measure: PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5
timeFrame: 48 months
measure: PK Parameter: Finding half-life of ZN-d5
timeFrame: 48 months
measure: PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5
timeFrame: 48 months
measure: Assess the hematologic response to ZN-d5
timeFrame: 48 months
measure: Duration and time to hematologic response to ZN-d5
timeFrame: 48 months
Other outcomes:
measure: To assess potential biomarker of ZN-d5
timeFrame: 48 months
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Westmead
country: Australia
facility: Blackwater (Westmead) Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Nicosia
country: Cyprus
facility: Bank of Cyprus Hospital
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens
city: Haifa
country: Israel
facility: Rambam Hospital
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Barcelona
country: Spain
facility: ICO Badalona-H.U. Germans Trias i Pujol
state: Badalona
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Salamanca
country: Spain
facility: Clinico de Salamanca
Study officials:
affiliation: K-Group Alpha subsidiary of Zentalis Pharmaceuticals
name: Medical Affairs
role: STUDY_DIRECTOR
References: