Phase II Study of Combined Pirtobrutinib, Venetoclax and Obinutuzumab (PVO) Time-limited Treatment for Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

NCT06967610 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0271NCI-2025-03338
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the drug combination pirtobrutinib, venetoclax, and obinutuzumab can help to control relapsed CLL/SLL.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Leukemia (SLL)

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5

  Through study completion; an average of 1 year.

Study Arms (2)

V-Exposed

EXPERIMENTAL

Venetoclax Exposed: Treatment with Pirtobrutinib+Venetoclax+Obinutuzumab Q4W

Drug: Pirtobrutinib; Drug: Venetoclax; Drug: Obinutuzumab

V-Naive

EXPERIMENTAL

Venetoclax Naive: Treatment with Pirtobrutinib+Venetoclax+Obinutuzumab Q4W

Drug: Pirtobrutinib; Drug: Venetoclax; Drug: Obinutuzumab

Interventions

Pirtobrutinib DRUG

Given PO 200mg daily

V-Exposed; V-Naive

Venetoclax DRUG

Given PO daily

V-Exposed; V-Naive

Obinutuzumab DRUG

Given IV 100mg day 1, 900 mg day 2, 100mg days 8, 15

V-Exposed; V-Naive

Eligibility Criteria

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

You may not qualify if:

• Participants who experienced progression of disease according to 2018 iwCLL criteria while on venetoclax will be excluded.
• Patient with prior history of Richter's syndrome or current Richter's Syndrome.
• Participants with known hypersensitivity to any of the excipients of pirtobrutinib, venetoclax,obinutuzumab or to any intended study medications.
• Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.
• History of bleeding diathesis.
• Participants 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).
• History of stroke or intracranial hemorrhage within 6 months of enrollment.
• Participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonists.
• 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 participant's participation in this study or interpretation of study outcomes.
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified Tcell (CAR-T) therapy within 60 days of enrollment or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing:
• active graft versus host disease (GVHD);
• cytopenia from incomplete blood cell count recovery post-transplant;
• need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity \> Grade 1 from CAR-T therapy;
• ongoing immunosuppressive therapy (\> 20 mg prednisone or equivalent daily).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

pirtobrutinib; venetoclax; obinutuzumab

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

Central Study Contacts

Alessandra Ferrajoli, MD

CONTACT

713-792-2063; aferrajo@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 13, 2025
• Study Start: July 15, 2025
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2033
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (1)