Pirtobrutinib (LOXO-305) Consolidation for MRD Eradication in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) Treated With Venetoclax

NCT05317936 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0953NCI-2022-02427
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of LOXO-305 (pirtobrutinib) and venetoclax can help to control previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of undetectable (U) minimal residual disease (MRD) in the peripheral blood

  Assessed by next generation sequencing (NGS) at a threshold of 0.01% sensitivity. The rate of U-MRD will be reported separately for each cohort, along with the corresponding exact 95% confidence interval.

  Up to completion of cycle 24 (each cycle is 28 days)

Study Arms (1)

Pirtobrutinib+venetoclax

EXPERIMENTAL

Pirtobrutinib by mouth at the same time each day Venetoclax by mouth at the same time each day.

Drug: Pirtobrutinib; Drug: Venetoclax

Interventions

Pirtobrutinib DRUG

Given by PO

Also known as: LOXO-305

Pirtobrutinib+venetoclax

Venetoclax DRUG

GIven by PO

Also known as: ABT-199, GDC-0199

Pirtobrutinib+venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLL per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria
• Received venetoclax for at least 12 cycles, with MRD \> 0.01% detectable in peripheral blood, by Adaptive Biotechnologies NGS assay, within the month prior to study enrollment
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Serum bilirubin =\< 1.5 x upper limit of normal (ULN) or =\< 3 x ULN for patients with Gilbert's disease
• Serum creatinine clearance of \>= 30 ml/min (calculated or measured)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3.0 x ULN, unless clearly due to documented disease involvement, in which case ALT and AST =\< 5.0 x ULN
• Platelet count of \>= 50,000/ul, with no platelet transfusion in prior 2 weeks
• Absolute neutrophil count (ANC) \>= 1000/ul in the absence of growth factor support
• Hemoglobin \>= 8 mg/dL
• Activated partial thromboplastin time (aPTT) or partial thromboplastin time and prothrombin time (PT) or international normalized ratio (INR) not greater than 1.5 x ULN
• Ability to provide informed consent and adhere to the required follow-up
• Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use use both a highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc) during the period of therapy and for 6 months after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for \>= 1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug

You may not qualify if:

• Known or suspected Richter's transformation to diffuse large B cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin lymphoma at any time preceding enrollment
• Known or suspected history of central nervous system (CNS) involvement by CLL
• History of grade \>= 3 arrhythmia on prior covalent Bruton's tyrosine kinase (BTK) inhibitor
• Patients who experienced a major bleeding event on a prior BTK inhibitor
• \* NOTE: Major bleeding is defined as bleeding having one or more of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g/dL; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)
• Active second malignancy. Patients with a treated second malignancy and with likelihood of requiring systemic therapy within the next 2 years of \< 10%, as determined by an expert in the field, will be eligible. Examples include:
• Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
• Adequately treated cervical carcinoma in situ without current evidence of disease
• Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years and receiving adjuvant hormonal therapy
• Localized prostate cancer undergoing active surveillance
• History of treated and cured Hodgkin's disease or non-Hodgkin lymphoma (NHL) \< 5 years from diagnosis
• Major surgery within 4 weeks of planned start of study therapy
• A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disorder, that, in the opinion of the Investigator, would adversely affect the patient's participation in this study or interpretation of study outcomes
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor (CAR)-T therapy within the past 60 days or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing:
• Active graft versus host disease (GVHD)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

pirtobrutinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alessandra Ferrajoli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: April 8, 2022
• Study Start: November 16, 2022
• Primary Completion: October 6, 2025
• Study Completion: October 6, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (1)