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LeukemiaPhase 2NCT05536349

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

A Phase 2 study testing Pirtobrutinib, Obinutuzumab and Venetoclax in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Pirtobrutinib, Obinutuzumab and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
20 Dec 2022to 25 Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • Adequate renal function
  • 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.
  • 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

Who cannot join

  • 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
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  • 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.
  • 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)
  • 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
  • Grapefruit or grapefruit products
  • Seville oranges or products from Seville oranges
  • Star fruit 13. Current treatment with the following P-gp inhibitors: amiodarone, clarithromycin, cyclosporine, erythromycin, ketoconazole, and verapamil. A washout period of at least 5 half-lives of the inhibitor before study entry is required.
  • 14. Known central nervous system involvement by CLL/SLL/RT 15. Active second malignancy unless in remission and with life expectancy > 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin or carcinoma "in situ" of the cervix or breast who are eligible even if diagnosed within 2 years. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the Principal Investigator.
  • 16. Prior therapy restrictions
  • Cohort 1 (CLL/SLL)
  • Prior receipt of anti-CD20 monoclonal antibody therapy for non-malignant indication, including for autoimmune phenomenon ii. Prior receipt of systemic therapy for CLL/SLL
  • Cohort 2 (RT)
  • Patients who experienced a major bleeding event or grade ≥3 arrythmia on prior treatment with a BTK inhibitor ii. History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within 60 days of first dose of study drugs 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 or residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy
  • Ongoing immunosuppressive therapy (> 20 mg prednisone or equivalent daily) including GVHD prophylaxis/treatment (calcineurin inhibitors or ruxolitinib)
  • Patients are required to have the following washout periods prior to planned Cycle 1 Day 1 (C1D1). In addition, prior treatment-related AEs must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy.
  • 1. Targeted agents, investigational agents, therapeutic monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter
  • Immunoconjugated antibody treatment within 10 weeks prior to randomization
  • Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to study enrollment
  • Palliative limited field radiation must be completed 7 days prior to study enrollment.
  • Prior therapy with venetoclax and obinutuzumab is allowed but Richter should not have developed while actively receiving venetoclax or obinutuzumab (active therapy implies having received venetoclax or obinutuzumab within the prior 3 months)
  • 17. Known hypersensitivity to any component or excipient of study drugs
  • 18. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drugs
  • 19. Receipt of live-virus vaccines within 4 weeks prior to starting study drugs
  • 20. History of bleeding diathesis

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Nitin Jain, MD contact

(713) 745-6080

njain@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Nitin Jain, MD, 713-745-6080, njain@mdanderson.org

    Nitin Jain, MD

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

Primary Objective:

  1. Estimate the therapeutic activity (undetectable measurable residual disease [U-MRD] rate) of combined pirtobrutinib, venetoclax, and obinutuzumab in patients with previously untreated CLL/SLL (cohort 1) by undetectable measurable residual disease (U-MRD) rate and Richter transformation (cohort 2) by overall response rate (ORR) (defined as CMR//PMR).

Secondary Objectives:

  1. To estimate the therapeutic activity of combination therapy by determining:
  2. Combined response rate (defined as CR/CRi/PR) as assessed by the investigator for cohort 1 (CLL/SLL)
  3. Progression free survival (PFS) and overall survival (OS).
  4. U-MRD response with next generation sequencing assay for cohort 2
  5. To determine the safety and tolerability of this combination therapy

Exploratory Objective:

  1. To study immunological and molecular changes in the peripheral blood and bone marrow in response to pirtobrutinib, venetoclax, and obinutuzumab.
  2. To evaluate the kinetics of MRD response over time
Conditions
Leukemia
Being tested
Pirtobrutinib, Obinutuzumab, Venetoclax, Valacyclovir, Allopurinol
Medical subject headings
Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirtobrutinibDrug

    Given by PO

  • ObinutuzumabDrug

    Also called GA101, Gazyva, RO5072759

    Given by (IV) vein

  • VenetoclaxDrug

    Also called ABT-199, GDC-0199

    Given by PO

  • ValacyclovirDrug

    Given by PO

  • AllopurinolDrug

    Given by PO

Study groups in NCT05536349
Study groupRoleWhat they receive
Pirtobrutinib plus Venetoclax plus Obinutuzumab (combination)ExperimentalParticipants will receive the study drugs in cycles. Each cycle is 28 days.
Receives: Drug: Pirtobrutinib; Drug: Obinutuzumab; Drug: Venetoclax; Drug: Valacyclovir; Drug: Allopurinol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: through study completion an average of 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2022
  2. Study start20 Dec 2022
  3. Primary completion25 Apr 2028 (estimated)
  4. Study completion25 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05536349
Sponsor's protocol ID
2021-0578
Other IDs
NCI-2022-07625
Status last verified
Apr 2026
First submitted
7 Sep 2022
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirtobrutinib, Obinutuzumab and Venetoclax in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nitin Jain, MD ((713) 745-6080, njain@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: through study completion an average of 1 year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05536349.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

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Clinical Trial NCT05536349 | AzTrials