Time-limited Triplet Combination of Pirtobrutinib, Venetoclax, and Obinutuzumab for Patients With Treatment-naïve Chronic Lymphocytic Leukemia (CLL) or Richter Transformation (RT)

NCT05536349 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0578NCI-2022-07625
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of pirtobrutinib (also called LOXO-305), venetoclax, and obinutuzumab is safe and effective when given to patients with chronic lymphocytic leukemia (CLL) or Richter transformation (RT) who have not previously received treatment.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• The severity of the adverse events (AEs) will be graded according to the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

  through study completion an average of 1 year.

Study Arms (1)

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

EXPERIMENTAL

Participants will receive the study drugs in cycles. Each cycle is 28 days.

Drug: Pirtobrutinib; Drug: Obinutuzumab; Drug: Venetoclax; Drug: Valacyclovir; Drug: Allopurinol

Interventions

Allopurinol DRUG

Given by PO

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

Pirtobrutinib DRUG

Given by PO

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

Obinutuzumab DRUG

Given by (IV) vein

Also known as: GA101, Gazyva, RO5072759

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

Valacyclovir DRUG

Given by PO

Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of previously untreated CLL/SLL meeting iwCLL 2018 indication for treatment (cohort 1) or with a diagnosis of previously untreated or relapsed/refractory RT arising from CLL (cohort 2). Previously untreated patients with RT must have received prior therapy for CLL.
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2
• Adequate hepatic function
• Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease or documented disease involvement of liver (In pts with elevated total bilirubin due to increased indirect bilirubin, pts with direct bilirubin ≤1.5 x ULN are eligible)
• ALT and AST ≤3.0 x ULN, or ≤5.0 x ULN if documented disease involvement of liver
• Adequate renal function
• a. Creatinine clearance ≥ 50 ml/min (calculated using CKD-EPI formula)
• Adequate hematologic function a. Platelet count ≥50 x109/L and hemoglobin ≥ 8 g/dL (≥ 80 g/L). Platelet and hemoglobin requirements are independent of transfusions within 7 days of screening assessment and first dose of study drugs.
• b. Absolute neutrophil count ≥ 0.75 x 109/L. Absolute neutrophil count is independent of growth factor support within 7 days of screening assessment and first dose of study drugs.
• Ability to swallow tablets and comply with outpatient treatment, laboratory monitoring, and required clinic visit for the duration of study participation
• Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 6 months following the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal greater than 2 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug

You may not qualify if:

• Major surgery within 4 weeks prior to the first dose of study drugs
• Uncontrolled active systemic infection
• Known positive serology for human immunodeficiency virus (HIV)
• Active hepatitis B infection (defined as the presence of detectable HBV DNA, HBe antigen or HBs antigen). Patients with serologic evidence of prior vaccination (HBsAg negative, anti-HBs antibody positive, anti-HBc antibody negative) are eligible. Patients who are HBsAg negative/HBsAb positive but HBcAb positive are eligible, provided HBV DNA is negative and they are willing to take appropriate anti-viral prophylaxis
• Active hepatitis C infection (defined as detectable hepatitis C RNA in plasma by PCR)
• Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible
• Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with \> 20 mg daily of prednisone or equivalent or for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts
• Clinically significant, uncontrolled cardiovascular disease (≥3 NYHA heart failure, uncontrolled or symptomatic arrythmias), or myocardial infarction within 6 months, or stroke within 6 months, or intracranial bleeding within 6 months prior to start of study drugs
• Prolongation of the QT interval corrected for heart rate (QTcF) \> 470 msec. Note: Patients with QTcF \> 470 msec should have EKG repeated. If QTcF again is \> 470 msec, then the patient should be referred to cardiology for evaluation. Patient can be enrolled later if cleared by cardiology and repeat QTcF less than 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33) a. Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
• b. Correction for underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
• Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment
• Concurrent use of warfarin or another vitamin K antagonist
• Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. A washout period of at least 5 half-lives of these agents following discontinuation and prior to study entry is required (treatment with moderate CYP3A4 inhibitors or inducers is not excluded)
• a. Because of their effect on CYP3A4, use of any of the following within 7 days of study therapy start or planned use during study participation is prohibited
• i. Grapefruit or grapefruit products

Sponsors & Collaborators

• The Leukemia and Lymphoma Society: collaborator
• M.D. Anderson Cancer Center: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia

Interventions

pirtobrutinib; obinutuzumab; venetoclax; Valacyclovir; Allopurinol

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Nitin Jain, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nitin Jain, MD

CONTACT

(713) 745-6080; njain@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 10, 2022
• Study Start: December 20, 2022
• Primary Completion (Estimated): April 25, 2028
• Study Completion (Estimated): April 25, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)