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Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis

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ClinicalTrials.gov Identifier: NCT05199337
Recruitment Status : Recruiting
First Posted : January 20, 2022
Last Update Posted : October 6, 2022
Sponsor:
Information provided by (Responsible Party):
K-Group Alpha, Inc.

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.

Condition or disease Intervention/treatment Phase
Amyloidosis AL Amyloidosis Drug: ZN-d5 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2021
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arm Intervention/treatment
Experimental: Treatment Arm
Subjects will receive ZN-d5 orally (PO), once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: ZN-d5
ZN-d5 will be administered orally
Other Name: Study Drug




Primary Outcome Measures :
  1. 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

  2. Dose limiting toxicities [ Time Frame: 18 Months ]
    Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects


Secondary Outcome Measures :
  1. PK Parameter: Finding max concentration (Cmax) of ZN-d5 [ Time Frame: 48 months ]
    Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels.

  2. PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5 [ Time Frame: 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.

  3. PK Parameter: Finding half-life of ZN-d5 [ Time Frame: 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

  4. PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5 [ Time Frame: 48 months ]
    The total exposure of ZN-d5 over time (AUC) from the plasma collected by the subject at different dose levels.

  5. Assess the hematologic response to ZN-d5 [ Time Frame: 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.

  6. Duration and time to hematologic response to ZN-d5 [ Time Frame: 48 months ]
    The rate of, duration of, and time to CR, modified Complete Response (mCR), CR+VGPR, and mCR+VGPR


Other Outcome Measures:
  1. To assess potential biomarker of ZN-d5 [ Time Frame: 48 months ]
    The number of peripheral B-Cells from blood tests



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Adequate time since prior therapy before initiation of treatment (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);
  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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05199337


Contacts
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Contact: K-Group Alpha subsidiary of Zentalis Pharmaceuticals 858-263-4333 info@zenopharma.com

Locations
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United States, Colorado
Site 0198 Recruiting
Denver, Colorado, United States, 80218
United States, Louisiana
Site 0200 Recruiting
New Orleans, Louisiana, United States, 70112
United States, Missouri
Site 2404 Recruiting
Saint Louis, Missouri, United States, 63130
United States, Tennessee
Site 0199 Recruiting
Nashville, Tennessee, United States, 37203
Australia, New South Wales
Site 2711 Recruiting
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Site 2712 Recruiting
Brisbane, Queensland, Australia, 4102
Australia, South Australia
Site 2714 Recruiting
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
Site 2713 Not yet recruiting
Nedlands, Western Australia, Australia
Greece
Site 4101 Recruiting
Athens, Greece, 115 28
Israel
Site 3804 Recruiting
Haifa, Israel, 3109601
Site 3804 Recruiting
Haifa, Israel
Site 3805 Recruiting
Jerusalem, Israel
Site 3802 Recruiting
Ramat Gan, Israel
Spain
Site 3502 Recruiting
Barcelona, Badalona, Spain
Site 3507 Recruiting
El Palmar, Murcia, Spain, 30120
Site 3509 Recruiting
Barcelona, Spain, 08036
Site 3506 Recruiting
Salamanca, Spain
Sponsors and Collaborators
K-Group Alpha, Inc.
Investigators
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Study Director: Anthony Fiorino, MD, PhD K-Group Alpha subsidiary of Zentalis Pharmaceuticals
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Responsible Party: K-Group Alpha, Inc.
ClinicalTrials.gov Identifier: NCT05199337    
Other Study ID Numbers: ZN-d5-003
First Posted: January 20, 2022    Key Record Dates
Last Update Posted: October 6, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by K-Group Alpha, Inc.:
Amyloidosis
AL Amyloidosis
RRAL
BCL2 Inhibitor
t(11;14)
ZN-d5
Light Chain Amyloidosis
Light chain (AL) Amyloidosis
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias