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A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

RecruitingPhase 2

A Phase 2, Open-Label, Randomized Study Evaluating the Efficacy and Safety of 3 Doses of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Who Previously Received Treatment With a Covalent Bruton Tyrosine Kinase Inhibitor

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

* Have confirmed diagnosis of CLL/SLL as defined by iwCLL 2018 criteria.
* Part 1: Have received prior CLL/SLL treatment
* Have received at least 1, but not more than 3 lines of prior treatment for CLL/SLL
* Have received a covalent BTK inhibitor
* Part 2: Have received no prior treatment for CLL/SLL

  * Part 1 - Known 17p deletion status (positive or negative)
  * Part 2 - Must have 17p deletion (positive)
* Have a requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy
* Capable of swallowing oral study medication.
* Have an Eastern Cooperative Oncology Group Performance Status (ECOG) score of 0 to 2.

Exclusion Criteria:

* Have received prior treatment with a BTK degrader or a noncovalent BTK inhibitor
* Have a history of greater than or equal to (\>=) Grade 3 bleeding due to treatment with a BTK inhibitor
* Have known or suspected Richter's transformation
* Have known or suspected history of central nervous system involvement by CLL/SLL
* Previous or concurrent cancer distinct from CLL/SLL within 3 years before randomization. Exceptions may occur with documented sponsor approval. Examples include:

  * nonmelanoma skin cancer or lentigo malignant melanoma
  * cervical carcinoma in situ
  * localized prostate cancer undergoing active surveillance, and
  * localized (for example, lymph node negative) breast cancer with no evidence of active disease present for more than 3 years. Individual may be receiving adjuvant hormonal therapy

About the study

The main purpose of Part 1 of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The purpose of Part 2 of this study is to evaluate pirtobrutinib monotherapy in participants with treatment-naïve CLL/SLL with 17p deletions. Participation in Part 1 is expected to last approximately 3 years. Participation in Part 2 is expected to last up to 2 years.

What is being tested

Sponsor: Loxo Oncology, Inc. · Participants: 249 · Started: Jan 3, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06588478

Locations in the U.S.

ArizonaIronwood Cancer & Research Centers, Chandler
CaliforniaCity of Hope National Medical Center, Duarte
City of Hope National Medical Center, Irvine
Palo Alto Medical Foundation Research Institute (PAMFRI), Palo Alto
Stanford Cancer Center, Palo Alto
ColoradoRocky Mountain Cancer Center, Aurora
FloridaUniversity of Miami Hospital and Clinics, Sylvester Cancer Center, Miami
GeorgiaCity of Hope National Medical Center, Atlanta Cancer Center, Newnan
IowaMission Cancer + Blood, Waukee
KentuckySaint Elizabeth Medical Center Edgewood, Edgewood
MarylandAmerican Oncology Partners, PA, Bethesda
MassachusettsBoston Medical Center, Boston
MississippiGulfport Memorial Hospital, Gulfport
NevadaComprehensive Cancer Centers of Nevada, Henderson
North CarolinaEast Carolina University, Greenville
OregonWilliamette Valley Cancer Institute & Research Center, Eugene
PennsylvaniaCancer Care Associates Of York, York
TennesseeThe West Clinic, PLLC dba West Cancer Center, Germantown
TexasUSO-Texas Oncology-Central/South Texas, Austin
Sarah Cannon Research Institute/SCRI, The Woodlands
VirginiaUSO-Virginia Oncology Associates, Hampton

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.