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New treatment option for Mantle Cell Lymphoma
Official title Phase II Study of Pirtobrutinib With Venetoclax In Relapsed-Refractory MCL (Mantle Cell Lymphoma) Patients
ClinicalTrials.gov ID: NCT05529069
What this study is testing
What is Pirtobrutinib?
Pirtobrutinib is an investigational medicine, being studied as a potential treatment for mantle cell lymphoma.
Also referred to as LOXO-305.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- To learn if the combination of pirtobrutinib (also called LOXO-305) and venetoclax can help to control mantle cell lymphoma (MCL) that is relapsed (has come back) or refractory (has not responded to therapy).
- Phase 2: a mid-size study of how well it works
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Confirmed diagnosis of mantle cell lymphoma in tissue biopsy by hematopathology with/without chromosome translocation t(11;14), (q13;q32) and/or...
- The patient is able to take oral medications
- Relapsed MCL (irrespective of prognostic factors) including any lines or prior therapy or patients who had prior ibrutinib, acalabrutinib...
- Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent...
- Age from \>=18 years at the time of signing the informed consent.
You likely can't join if
- Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and...
- History of bleeding diathesis
- History of stroke or intracranial hemorrhage within 6 months of C1D1
- Vaccination with live vaccine within 28 days prior to enrollment.
- Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to the intended covalent BTK inhibitor if assigned by chance to control...
- Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. NOTE: Major bleeding is defined as...
See the full eligibility criteria
Who can join
- Confirmed diagnosis of mantle cell lymphoma in tissue biopsy by hematopathology with/without chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy. Cyclin D1 negative MCL (confirmed...
- The patient is able to take oral medications
- Relapsed MCL (irrespective of prognostic factors) including any lines or prior therapy or patients who had prior ibrutinib, acalabrutinib, zanubrutinib, other BTK inhibitor or anti CD19-CART therapy, single agent or in...
- Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
- Age from \>=18 years at the time of signing the informed consent.
- Patients may have at least 1 site of radiographically assessable disease (i.e., lymph node longest diameter [LDi] \>= 1.5 cm, not necessary for disease assessable by positron emission tomography [PET]/computerized...
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
- Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate...
- Patients must have relapsed or refractory MCL (irrespective of prior BTK inhibitor or anti CD19 CART exposure).
- Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 times the institutional upper limit of normal range (patients with an elevated prothrombin time and known lupus...
- Adequate BM function independent of growth factor or PRBC or platelet transfusion support (within 14 days of Screening assessment and criteria must be met on C1D1 without transfusion/G-CSF within 7 days of assessment...
- platelet count \>=50, 000/mm3;
- absolute neutrophil count (ANC) \>= 1000/mm3 unless cytopenia is clearly due to marrow involvement from MCL
- total hemoglobin \>= 8 g/dL (without transfusion support within 2 weeks of screening); If any of the above-mentioned cytopenias (a-c) are present due to significant BM involvement, at least 30% BM involvement by MCL...
- Adequate organ function as defined by the following laboratory values:
- Creatinine clearance. \>=30 mL/min (by Cockcroft-Gault method, APPENDIX I),
- Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement and/or Gilbert's Disease or controlled immune hemolysis or considered an effect of regular blood transfusions.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 x ULN, or \< 5 x upper limit of normal if hepatic metastases are present.
- Projected life expectancy of \>12 weeks pertaining to lymphoma.
- Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have confirmed negative results for a pregnancy test at screening, on a blood or urine sample obtained within 7 days prior to...
- Women of childbearing potential and men with female partners of childbearing potential must be willing to use an effective form of contraception for at least 6 months after the last dose of study treatment. Patient...
- Hormonal contraception (birth control pills, patches, or rings)
- Intrauterine device (IUD)
- Birth control injections
- Double barrier methods (diaphragm with spermicidal gel or condoms with birth control foam)
- Sterilization of participant or partner ("tubes tied" or vasectomy) Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal [and 2 years of non-therapy-induced...
- Periodic abstinence (calendar, hypothermal, or post-ovulation methods)
- Withdrawal (coitus interruptus)
- Spermicide only
- Lactational amenorrhea method Sperm donation is prohibited during the duration of participation on this protocol and for 6 months after the last dose of any study drug.
- Patients are required to have the following washout periods prior to planned Cycle 1 Day 1 (C1D1).
- Targeted agents, investigational agents, therapeutic monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter
- Immunoconjugates antibody treatment within 10 weeks prior to enrollment.
- Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must be completed 28 days prior to study enrollment
- Palliative limited field radiation must be completed 7 days prior to study enrollment. Note: In the case of known central nervous system (CNS) involvement by systemic lymphoma: Patients with previous treatment for CNS...
- Prior treatment-related AEs must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy.
What rules you out
- Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease (as shown by MRI brain and/or CSF or...
- History of bleeding diathesis
- History of stroke or intracranial hemorrhage within 6 months of C1D1
- Vaccination with live vaccine within 28 days prior to enrollment.
- Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to the intended covalent BTK inhibitor if assigned by chance to control arm.
- Patients 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...
- Pregnant or lactating females.
- Known and uncontrolled HIV infection. Participants with HIV (known HIV 1/2 antibodies positive) are allowed if all of the following conditions are met:
- CD4+ T-cell counts ≥350 cells/μL;
- Participants with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections may be eligible, if they have not had an opportunistic infection within the past 12 months;
- If participant is on antiretroviral, evaluation of the specific agents must be performed in order to determine if participant is eligible (e.g., excluding patients taking strong CYP3A inhibitors such as ritonavir). If...
- Screening for HIV infection is not required
- 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...
- Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other...
- Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment
- Significant cardiovascular disease defined as:
- unstable angina or acute coronary syndrome within the past 2 months prior to enrollment
- history of myocardial infarction within 3 months prior to enrollment or
- documented LVEF by any method of ≤ 40% in the 12 months prior to enrollment
- ≥ Grade 3 NYHA functional classification system of heart failure, uncontrolled or symptomatic arrhythmias
- 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 ECG, during Screening. QTcF is calculated using...
- 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...
- 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.
- Concomitant malignancies or previous malignancies with less than a 1-year disease-free interval at the time of signing consent. people with adequately treated basal or squamous cell carcinoma of the skin, or adequately...
- a. Adequately treated no melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease.
- b. Adequately treated cervical carcinoma in situ without current evidence of disease.
- c. 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.
- d. Localized prostate cancer undergoing active surveillance.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel...
- With known allergies to xanthine oxidase inhibitors and/or rasburicase.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risk associated with study participation or study treatment...
- No concomitant anticancer therapies, immunotherapies, cellular, or radiotherapy. No major surgery within 4 weeks prior to first dose of study treatment. Washout period for chemotherapy is 14 days. Washout period for...
- Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) is for which...
- Concomitant steroids for disease related pain control are allowed at any dose but must be discontinued prior to any study treatment initiation. Chronic use of corticosteroids is allowed up to 20 mg prednisone or...
- History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within 60 days of enrollment or presence of any of the following, regardless of prior SCT...
- Known neurologic disorder or residual neurologic toxicities that may put patients at increased risk of neurologic toxicity in the opinion of the investigator.
- Active uncontrolled systemic infection.
- Received an investigational agent within 2 weeks or within 5 T1/2, whichever is shorter prior to the first dose of study treatment.
- Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors. Because of their effect on CYP3A4, use of any of the following within 3 days of study therapy...
- Seville oranges or products from Seville oranges
- star fruit
- Patients taking warfarin and/or equivalent vitamin K antagonists are excluded since the use of these agents is contraindicated with Pirtobrutinib or with venetoclax.
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.