Lymphoma, Mantle-Cell
Conditions
Keywords
Bruton's Tyrosine Kinase Inhibitor, BTKi, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-Cell, Lymphoma, pirtobrutinib
Brief summary
This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.
Detailed description
This is a Phase 3 global, randomized, open-label study comparing pirtobrutinib (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.
Interventions
DRUGPirtobrutinib
Oral
DRUGIbrutinib
Oral
DRUGAcalabrutinib
Oral
DRUGZanubrutinib
Oral
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed MCL diagnosis * Previously treated with at least one prior line of systemic therapy for MCL * Measurable disease per Lugano criteria * Eastern Cooperative Oncology Group (ECOG) 0-2 * Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening * Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening * Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening. * AST and ALT ≤ 3.0 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN. * Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula
Exclusion criteria
* Prior treatment with an approved or investigational BTK inhibitor * History of bleeding diathesis * History of stroke or intracranial hemorrhage within 6 months of randomization * History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization * Clinically significant cardiovascular disease * Prolonged QT interval corrected using Fridericia's formula (QTcF) \> 470 ms on 2/3 consecutive ECGs, and mean QTcF\>470 ms on all 3 ECGs * Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible) * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption * Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment. * Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist. * Vaccination with live vaccine within 28 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL) | Up to approximately 24 months | Assessed per Lugano criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms | Up to approximately 24 months | Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death |
| To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms | Up to approximately 24 months | Time from randomization to time when discontinuation criteria met |
| Time to worsening (TTW) of MCL-related symptoms | Up to approximately 24 months | Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms. |
| Comparative Tolerability as measured by proportion of time with high side effect burden | Up to approximately 24 months | Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome. |
| To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms | Up to approximately 24 months | Assessed per Lugano criteria |
| To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms | Up to approximately 24 months | Assessed per Lugano criteria |
| To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms | Up to approximately 24 months | Assessed by survival |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORPatient Advocacy
Loxo Oncology, Inc.
Outcome results
None listed