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RecruitingInterventionalPhase 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

NCT ID: NCT06588478Sponsor: Loxo Oncology, Inc.Last updated: 2026-05-19

Summary

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.

Arms & interventions

  • DrugPirtobrutinib

    Administered Orally.

Outcome measures

Primary

  • Overall Response Rate

    Overall response rate is defined as the proportion of participants who achieve the best overall response at or before the initiation of subsequent anticancer therapy of CR, CRi, nPR, or PR. ORR will be assessed using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 response criteria.

    Time frame: Baseline up to 3 years

Secondary

  • Duration of Response

    Time frame: Baseline up to 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (21)

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224

Recruiting
Michael Musci · Principal Investigator

City of Hope National Medical Center

Duarte, California, 91010

Recruiting
· Contact
Alexey Danilov · Principal Investigator

City of Hope National Medical Center

Irvine, California, 92618

Recruiting
· Contact
Alexey Danilov · Principal Investigator

Palo Alto Medical Foundation Research Institute (PAMFRI)

Palo Alto, California, 94304

Recruiting
Roozbeh Mohajer · Principal Investigator

Stanford Cancer Center

Palo Alto, California, 94304

Recruiting
Bita Fakhri · Principal Investigator

Rocky Mountain Cancer Center

Aurora, Colorado, 80012

Recruiting
· Contact
John Burke · Principal Investigator

University of Miami Hospital and Clinics, Sylvester Cancer Center

Miami, Florida, 33136

Recruiting
Alvaro Alencar · Principal Investigator

City of Hope National Medical Center, Atlanta Cancer Center

Newnan, Georgia, 30265

Recruiting
Sabarish Ayyappan · Principal Investigator

Mission Cancer + Blood

Waukee, Iowa, 50263

Recruiting
· Contact
Tara Graff · Principal Investigator

Saint Elizabeth Medical Center Edgewood

Edgewood, Kentucky, 41017

Recruiting
Miguel Islas-Ohlmayer · Principal Investigator

American Oncology Partners, PA

Bethesda, Maryland, 20817

Recruiting
· Contact
Victor Priego · Principal Investigator

Boston Medical Center

Boston, Massachusetts, 02118

Recruiting
Andrew Wilks · Principal Investigator

Gulfport Memorial Hospital

Gulfport, Mississippi, 39501

Recruiting
· Contact
Pamela Tuli · Principal Investigator

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074

Recruiting
Anthony Nguyen · Principal Investigator

East Carolina University

Greenville, North Carolina, 27834

Recruiting
· Contact
Darla Liles · Principal Investigator

Williamette Valley Cancer Institute & Research Center

Eugene, Oregon, 97401

Recruiting
· Contact
Jeff Sharman · Principal Investigator

Cancer Care Associates Of York

York, Pennsylvania, 17403

Recruiting
· Contact
Jackson Gao · Principal Investigator

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, 38138

Recruiting
· Contact
Jason Chandler · Principal Investigator

USO-Texas Oncology-Central/South Texas

Austin, Texas, 78705

Recruiting
· Contact
Jason Melear · Principal Investigator

Sarah Cannon Research Institute/SCRI

The Woodlands, Texas, 77380

Recruiting
· Contact
SMO Sarah Cannon Research Inst. · Principal Investigator

USO-Virginia Oncology Associates

Hampton, Virginia, 23666

Recruiting
· Contact
Celesteann Bremer · Principal Investigator