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New treatment option for Non Hodgkin Lymphoma
Official title LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies
ClinicalTrials.gov ID: NCT05990465
What this study is testing
What is Pirtobrutinib?
Pirtobrutinib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for non hodgkin lymphoma.
Also referred to as Jaypirca, 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
- This is a phase I, interventional, single arm, open label, treatment study designed to evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and maintenance in adult patients with B cell malignancies that have failed prior therapies.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 81
You may be able to join if
- To facilitate rapid start of pirtobrutinib, there will be separate inclusion/exclusion for pirtobrutinib and LV20.19 CAR T-cells in addition to the...
- Patients must be aged ≥18 years and \<81 years with relapsed or refractory B-cell non-Hodgkin Lymphoma (NHL).
- Diagnosis of relapsed or refractory B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell...
- Disease specific criteria as follows:
- DLBCL and associated subtypes (listed above) i. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody with...
You likely can't join if
- A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.
- Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential or plan to become pregnant during the study or within 1 month...
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
- HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and...
- Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for...
- Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible).
See the full eligibility criteria
Who can join
- To facilitate rapid start of pirtobrutinib, there will be separate inclusion/exclusion for pirtobrutinib and LV20.19 CAR T-cells in addition to the general inclusion as outlined below. General for trial:
- Patients must be aged ≥18 years and \<81 years with relapsed or refractory B-cell non-Hodgkin Lymphoma (NHL).
- Diagnosis of relapsed or refractory B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell Lymphoma, Burkitt Lymphoma and DLBCL with associated subtypes (aggressive...
- Disease specific criteria as follows:
- DLBCL and associated subtypes (listed above) i. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody with combination anthracycline based chemotherapy regimen and have ONE of the...
- Primary refractory lymphoma or early relapse ≤6 months after one line of therapy.
- For relapse \>6.00 months, failure of two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. ii. Relapse post-autologous transplant. iii. Relapse...
- Relapsed disease after two lines of cytotoxic chemotherapy including administration of anti-CD20 antibody.
- Progressive disease after ≥second line BTK inhibitor.
- Relapse post-autologous transplant.
- Relapse post-allogeneic transplant. c. Marginal Zone Lymphoma and Follicular Lymphoma i. Must have received Rituximab or another CD20 antibody with chemotherapy regimen appropriate for the disease and have ONE of the...
- Relapsed disease after two lines of therapy including administration of anti-CD20 antibody.
- Relapse post-autologous transplant.
- Relapse post-allogeneic transplant. d. Burkitt's Lymphoma i. Must have received Rituximab or another CD20 antibody in combination with anthracycline based chemotherapy regimen and have ONE of the following:
- Primary refractory lymphoma.
- Relapse within 6 months.
- For relapse \>6 months, failure of two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. i. Relapse post-autologous transplant. ii. Relapse post-allogeneic...
- Able to provide written informed consent.
- Negative urine or serum pregnancy test in females of childbearing potential at screening.
- Willingness of women of reproductive potential and their partners to observe highly effective birth control methods for duration of treatment and for 1 month following the last dose if study treatment.
- Karnofsky performance score ≥70.
- Expected survival \>12 weeks.
- Patient has demonstrated compliance with prior therapies.
- Able to take oral medications.
- Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x upper limit of...
- Patients are required to have the following washout periods prior to planned Cycle 1 Day 1 (C1D1). In addition, prior treatment-related adverse events (AEs) must have recovered to Grade ≤ 1 with the exception of...
- 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. to START Pirtobrutinib Bridging:
- Absolute neutrophil count (ANC) ≥1000 with no G-CSF within 7 days or pegylated G-CSF within 14 days unless patient has biopsy proven bone marrow involvement.
- Platelets≥50,000 with no transfusion within 7 days unless patient has biopsy proven bone marrow involvement.
- Hemoglobin ≥8g/dL (≥80 g/L) [blood transfusions are allowable to reach this goal].
- Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine transaminase (ALT) \<3 x upper limit of normal (ULN) or \< 5 x ULN with documented liver involvement; serum bilirubin \<1.5 x ULN or \<3...
- Adequate renal function, defined as creatinine clearance≥50 ml/min.
- No IV hydration within 24 hours of eligibility.
- No dialysis dependent renal failure. for Pirtobrutinib Maintenance (part B)
- Recovery of neutrophils count after CAR T-cell infusion with ANC ≥1000/dL without G-CSF within the last 7 days.
- Recovery of platelet count after CAR T-cell infusion with platelet count ≥50,000/dL.
- Adequate hepatic function, defined as back to baseline or AST and ALT \<3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<3 x ULN, or considered not clinically significant as per the clinical...
- Adequate renal function, defined as creatinine clearance≥40 ml/min.
- Evidence of response or stable disease (complete response/partial response/stable disease) at day 28 after CAR T-cell therapy. for Apheresis and LV20.19 CAR T-cells:
- Active Measurable disease must be documented within 4 weeks of lymphodepletion start defined as nodal lesions greater than 15 mm in the long axis or extranodal lesions \>10 mm in long and short axis OR bone marrow...
- Absolute cluster of differentiation (CD) 3 count≥50 mm\^3.
- MRI brain and Lumbar Puncture with cerebrospinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement ONLY in patients with history of CNS involvement or...
- Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥45% (by echocardiogram (ECHO) or MUGA) and adequate pulmonary function as...
- No contraindication to central line access.
- ANC≥1000 with no pegylated G-CSF within 14 days unless patient has biopsy proven bone marrow involvement.
- Platelets≥50,000 with no transfusion within 72 hours unless patient has biopsy proven bone marrow involvement.
- Adequate hepatic function, defined as AST and ALT \<3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<3 x ULN, or considered not clinically significant as per the clinical PIs discretion (e.g...
- Adequate renal function, defined as creatinine clearance≥50 ml/min. a. No IV hydration within 24 hours of eligibility. b. No dialysis dependent renal failure.
What rules you out
- A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.
- Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential or plan to become pregnant during the study or within 1 month of the last dose of study treatment and women who are current lactating...
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
- HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation...
- 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 randomization. Patients who are...
- Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible).
- History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
- Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any previous treatment unless it is felt to be due to underlying disease.
- Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution. Minimum of 14 days or 5 half-lives of the drug (whichever is shorter) washout prior to...
- Refusal to participate in the long-term follow-up protocol.
- Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
- Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment and a remission documented within 8 weeks of planned CAR-T cell infusion by MRI...
- Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are \<100 days post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are...
- Prior allogeneic CAR T-cell therapy \<100 days from prior CAR T-cell treatment.
- Previous recipients of autologous CAR-T cell therapy directed at either cluster of differentiation 19 (CD19) or CD20 are excluded if they are \ 5% residual circulating CAR-T as measured by flow cytometry using a CD19...
- Anti-CD20 antibody treatment within 4 weeks of cell infusion.
- Anti-CD19 antibody treatment within 4 weeks of cell infusion.
- Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than replacement dose steroids) within 7 days prior to apheresis collection for CAR-T cells.
- No other oral chemotherapeutic agents or antibody directed treatment after starting pirtobrutinib other than steroids or radiation to a single site in a palliative fashion.
- Patients post solid organ transplant who develop high grade lymphomas or leukemias.
- Concurrent active malignancy other than basal or squamous cell carcinomas of the skin (underlying low-grade lymphoma chronic lymphocytic leukemia/Follicular lymphoma (FL) / Marginal zone lymphoma (MZL) is allowable in...
- Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
- History of stroke or intracranial hemorrhage within 6 months of randomization.
- Significant cardiovascular disease defined as myocardial infarction within 6 months of randomization, congestive heart failure with ejection fraction \ 470 msec on ECG.
- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug.
- Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
- Patients who had surgery within 4 weeks prior to randomization.
- Patients who have received vaccination with live vaccine within 28 days prior to randomization.
- Patients with known hypersensitivity to any of the excipients of pirtobrutinib. Special Criteria Regarding Fertility and Contraception Female people of reproductive potential (women who have reached menarche or women...
- Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally
- Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Vasectomized partner
- Sexual abstinence: considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual...
- Female sterilization
- Fallopian tube implants (if confirmed by hysterosalpingogram) Oocyte donation is prohibited during the duration of participation on this protocol and for 1 month after the last dose of study drug. people who are not of...
The study team makes the final eligibility decision.
Where it's taking place
- Milwaukee, Wisconsin, 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 to 81 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Milwaukee, Wisconsin, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
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.