Pirtobrutinib and Venetoclax in Waldenström Macroglobulinemia

Running, not enrolling · Phase 2

Conditions studied: Waldenstrom Macroglobulinemia

In brief

This study is being done to examine the safety and effectiveness of pirtobrutinib combined with venetoclax as a possible treatment for participants with Waldenström Macroglobulinemia (WM). The names of the study drugs involved in this study are: * Pirtobrutinib (a Noncovalent Bruton Tyrosine Kinase (BTK) inhibitor) * Venetoclax (a BCL2 inhibitor)

Key facts

Study ID

NCT05734495

Run by

Dana-Farber Cancer Institute

People needed

46

Starts

2023-05-02

Expected to finish

2033-01-25

Last updated by the study team

2026-05-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1.
• Clinicopathological diagnosis of Waldenström Macroglobulinemia, including MYD88 Wild-Type.
• At least 1 prior line of treatment.
• Prior covalent BTK inhibitor is allowed even if prior progression documented on this agent.
• Prior venetoclax is allowed unless participant had documented progression while on this agent.
• Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM. At least one of the following:
• -Constitutional Symptoms
• Recurrent fever
• Night sweats
• Fatigue
• Weight loss
• Progressive or symptomatic lymphadenopathy or splenomegaly
• Hemoglobin ≤ 10 g/dL
• Platelet count ≤ 100 k/uL
• Hyperviscosity syndrome
• Symptomatic peripheral neuropathy
• Systemic amyloidosis
• Renal Insufficiency
• Symptomatic cryoglobulinemia
• Age 18 years or older
• Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum serum IgM level of > 2 times the upper limit normal.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Women of childbearing potential: Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 6 months after discontinuation from the study. FCBP must be referred to a qualified provider of contraceptive methods if needed.
• Men must agree to use a latex condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy 1) while participating in the study; and 2) for at least 6 months after discontinuation from the study.
• Participants must have normal organ and marrow function as defined below:

You may not qualify if…

• Prior exposure to non-covalent BTK inhibitors
• Participants who experienced a major bleeding event or grade > 3 arrhythmia on prior treatment with a BTK inhibitor. NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g. retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome).
• Participants who are receiving any other investigational agents.
• Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed while enrolled in this study or within 6 months of last dose of study drug.
• Participants with known CNS lymphoma.
• Participants with known history of Human Immunodeficiency Virus (HIV) and known active cytomegalovirus (CMV) infection.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (antiHBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded.
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded.
• Concurrent administration of warfarin.
• Concurrent administration of moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong p-glycoprotein (P-gp) inhibitors
• Concurrent systemic immunosuppressant therapy. System steroids at doses <20mg prednisone per day are permitted.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
• Major surgery within 4 weeks of first dose of study drug.
• Malabsorption syndrome or other condition that precludes enteral route of administration.
• Participants with known history of alcohol or drug abuse.
• Participants with inability to swallow pills and inability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of the study participation
• Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts.
• Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs, during Screening. QTcF is calculated using Fridericia's Formula (QTcF): QTcF=QT/(RR0.33).
• 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
• Significant cardiovascular disease defined as:
• Unstable angina, or
• History of myocardial infarction within 6 months prior to planned start of pirtobrutinib, or

Where it is running

• Beth Israel Deaconness Medical — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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