An Extension Study for Patients Previously Enrolled in Studies With Pelabresib

Official title

An Open-Label, Multicenter, Extension Study for Patients Previously Enrolled in Studies With Pelabresib

Overview

The purpose of this study is to evaluate the long-term safety and the clinical benefit of pelabresib in patients with hematological and/or solid tumor indications or advanced malignancies. Additionally, participants previously enrolled in studies with pelabresib who received placebo or participants who discontinued pelabresib (for any other reason than participating in this extension study), may be enrolled in this extension study to evaluate the survival and leukemia-free survival (for patients with hematological malignancies) or only the Survival Follow-up (for all the other patients).

Detailed description

The study will collect and monitor ongoing efficacy information with regard to disease and survival status, as well as safety information with regard to AEs, including SAEs and AEs of special interest (AESI).

Patients are eligible to continue pelabresib treatment as long as the regimen is tolerated, and the patient does not meet any of the discontinuation criteria.

There will be an eligibility check period of up to 28 days for this extension study. Patients who fulfill the inclusion and exclusion criteria are eligible for the study. After the patient willingly provides consent, eligibility will be assessed by the investigator and treatment with pelabresib can be started at the same dose and dosing schedule that was applied in the parent study in the last cycle prior to EOT unless there is need for dose adjustment due to toxicity.

A patient is considered to have completed the study after completion of all visits as defined in the Schedule of Assessments (SoA) as per protocol, including the Safety Follow-up visit and Survival Follow-up.

The Safety Follow-up period is the interval between the EOT visit and the scheduled Safety Follow-up visit, which should occur 30 days (±3 days) after the last dose of pelabresib. For patients who switch from investigational pelabresib to commercial pelabresib treatment, the Safety Follow-up period is the time from the last dose of investigational pelabresib until the first dose of commercial pelabresib. The treatment start date with commercial pelabresib will be considered the date of "early Safety Follow-up termination." All patients will be followed for AEs and SAEs for 30 days (±3 days) following the last dose of pelabresib on the extension study or until the initiation of a new anticancer therapy, whichever occurs first.

Reasonable efforts should be made to have the patient return for the Safety Follow-up visit and review any AEs that may occur during this period. If the patient cannot return to the site for the Safety Follow-up visit, then the patient should be contacted by telephone for assessment of AEs.

The end of study will occur when all parent studies have been closed with no further patients expected to be enrolled into the extension study, and the last patient in the extension study has permanently discontinued study treatment (investigational pelabresib) and has completed the Safety Follow-up visit or is designated as lost to follow-up, died, or has withdrawn consent, whichever comes first. The sponsor reserves the right to close a study site or terminate the study at any time for any reason at the sole discretion of the sponsor.

Interventions

• Drug Pelabresib
  Small molecule inhibitor of bromodomain and extraterminal (BET) protein

Primary outcome measures

• Treatment-emergent adverse events (TEAEs) and serious TEAEs [Time frame: 5 years]
• Survival Follow-up [Time frame: 5 years]
• Duration of Response (DoR) [Time frame: 5 years]
• Progression-free survival (PFS) [Time frame: 5 years]
• Leukemia-free survival (LFS) [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Eligibility for Ongoing Pelabresib Treatment

• Able to provide signed informed consent, agreeing to all protocol and ICF requirements.
• At least 18 years old and legally able to consent in the study's jurisdiction.
• Previously enrolled and currently receiving pelabresib in a parent study.
• Demonstrating clinical benefit from pelabresib, as judged by the investigator.
• Willing and able to follow all study visits, treatments, and procedures.
• Agree to avoid pregnancy or fathering children:

• Men: Must use highly effective contraception (≥99% effective) and avoid sperm donation from eligibility check through 94 days post-treatment.
• Women of childbearing potential (WOCBP): Must test negative for pregnancy at eligibility, use highly effective contraception through 184 days post-treatment, undergo regular pregnancy testing, and avoid breastfeeding and oocyte donation during this period.
• Women not of childbearing potential (surgically sterile or postmenopausal ≥12 months without other cause) are eligible.

Note: Women with amenorrhea due to chemo/radiotherapy are considered WOCBP and must use contraception.

• Eligibility for Survival Follow-up

• Provide signed informed consent, agreeing to all protocol and ICF requirements.
• Are at least 18 years old and legally able to consent.
• Were previously enrolled in a pelabresib clinical study.
• Are willing and able to comply with follow-up procedures.

Exclusion criteria

• Eligibility for Ongoing Pelabresib Treatment

• Legally institutionalized or under judicial protection.
• Enrolled in another interventional clinical trial (excluding the parent study).
• History of hypersensitivity to pelabresib, its excipients, or similar drugs.
• Significant gastrointestinal issues (e.g., active IBD, unresolved nausea/vomiting/diarrhea > Grade 1) that may affect drug absorption.
• Any medical condition deemed unsuitable by the investigator.
• Uncontrolled illness or condition that may compromise safety or protocol compliance.
• Received systemic anticancer or investigational treatment (excluding parent study drug or hormonal therapy) within 2 weeks or 5 half-lives before first dose. (Hydroxyurea/anagrelide allowed up to 24 hours prior.)
• Received hematopoietic growth factors or androgenic steroids within 4 weeks before first dose.
• Used strong CYP3A4 inhibitors/inducers (e.g., St. John's wort) within 2 weeks before first dose. Use during treatment is prohibited.
• Female participants who are pregnant, breastfeeding, or not using required contraception.
• Male participants who do not agree to use contraception or refrain from sperm donation as specified.
• Unwilling or unable to comply with the study protocol.
• Eligibility for Survival Follow-up • They are legally institutionalized or under judicial protection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• University of California LA — Los Angeles
• Mayo Clinic Jacksonville — Jacksonville
• Northwestern University — Chicago
• Uni Of Michigan Health System — Ann Arbor
• New York Presbyterian Hospital — New York
• Mt Sinai Medical Center — New York

Italy · 3 centers

• Novartis Investigative Site — Florence
• Novartis Investigative Site — Varese
• Novartis Investigative Site — Novara

United Kingdom · 3 centers

• Novartis Investigative Site — Cardiff
• Novartis Investigative Site — Glasgow
• Novartis Investigative Site — London

Belgium · 2 centers

• Novartis Investigative Site — Antwerp
• Novartis Investigative Site — Bruges

Netherlands · 1 center

• Novartis Investigative Site — Amsterdam

Identifiers

NCT: NCT06401356 · CDAK539A12001B · CNST0610C210 · 2023-508950-24-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗