Clinical trial · Interventional

A Study to Investigate the Sequencing Strategy of Pirtobrutinib After Disease Progression on First-line Acalabrutinib Treatment for Adult Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

BOSS: BTK Inhibitor Optimal Sequencing Study Phase II Open-label Single Arm Trial of Pirtobrutinib in Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma After First-line Acalabrutinib Progression

NCT06839872CI-TRIAL-00090584BOSSwithdrawnPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): AstraZeneca has made the decision to cancel the trial.

Summary

Brief summary (as posted)

To assess the efficacy and safety of pirtobrutinib in participants with CLL/SLL who have progressed on first-line treatment with acalabrutinib.

Conditions

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Chronic Lymphocytic Leukemia	Chronic Lymphocytic Leukemia	ONTOLOGY_EXACT	0.98
Small Lymphocytic Lymphoma	Small Lymphocytic Lymphoma	ONTOLOGY_EXACT	0.98

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
Acalabrutinib	Drug	Acalabrutinib	ALIAS
Pirtobrutinib	Drug	Pirtobrutinib	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Pirtobrutinib and Acalabrutinib
description
Participants will receive dose A of pirtobrutinib starting Cycle 1 Day 1 for up to 24 cycles or until disease progression, unacceptable toxicity, death, or withdrawal of consent. If they progress on pirtobrutinib, a subset will receive dose B of acalabrutinib starting Cycle 1 Day 1 for up to 12 cycles or until disease progression, death, intolerance, unacceptable toxicity, or withdrawal of consent. Those benefiting from treatment will enter the Disease Follow-up period, continuing with pirtobrutinib or acalabrutinib until disease progression, unacceptable toxicity, death, or withdrawal of consent. After 36 months from starting pirtobrutinib, participants can continue receiving treatment off-trial if beneficial, in consultation with their physician.
interventionNames
1. Drug: Pirtobrutinib
2. Drug: Acalabrutinib

Primary outcomes (1)

measure
Objective Response Rate (ORR) in participants with CLL/SLL.
timeFrame
ORR will be assessed after 12 cycles (each cycle lasts 28 days) of pirtobrutinib.
description
ORR is defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per the iwCLL Criteria as assessed by the investigator.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 110 Years

Show eligibility criteria text

Inclusion Criteria:

* Participant must be ≥ 18 at the time of signing the informed consent.
* Participants must have received acalabrutinib monotherapy as first-line treatment for CLL/SLL, have progressed per the iwCLL Criteria (Hallek et al 2018) and be eligible for second-line treatment by the same criteria.
* ECOG performance status of 0, 1, or 2.
* Adequate organ and BM function.
* Adequate coagulation, defined as aPTT or PTT and PT or INR not greater than 1.5 × ULN.
* Participants have a clearly defined, documented and accessible start date of their first line acalabrutinib monotherapy for CLL/SLL.
* Participants are eligible for the acalabrutinib retreatment phase only if they have progressed on pirtobrutinib monotherapy per iwCLL Criteria.

Exclusion Criteria:

* Major surgical procedure within 30 days before and not recovered adequately the first dose of study drug.
* Participants who experienced a major bleeding event or Grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
* History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
* History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
* Significant cardiovascular disease.
* History of PML.
* Any active significant infection.
* HIV positive
* Active HBV or HCV infection.
* Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression.
* Active auto-immune cytopenia.
* History of prior or current malignancy.
* Requires or receiving therapeutic anticoagulation with warfarin or equivalent vitamin K antagonists.
* Received a live virus vaccination within 28 days of first dose of study drug.
* Requires treatment with a strong CYP3A inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited.

References

Publications (0)

Data not yet available

No reference posted for this study.