Clinical Trials List
Protocol NumberLOXO-BTK-20019 (J2N-OX-JZNM)
NCT Number(ClinicalTrials.gov Identfier)NCT04662255
2021-03-17 - 2025-06-15
Phase III
Recruiting4
A Phase 3 Open-Label, Randomized Study of LOXO-305 versus Investigator Choice of BTK Inhibitor in Patients with Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Loxo Oncology, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2023/03/10
Investigators and Locations
Co-Principal Investigator
- Jeng-Shiun Du Division of Hematology & Oncology
- Shih-Feng Cho Division of Hematology & Oncology
- 高育青 Division of Hematology & Oncology
- Hui-Ching Wang Division of Hematology & Oncology
- Yi-Chang Liu Division of Hematology & Oncology
- Tsung-Jang Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Liang-Tsai Hsiao Division of Hematology & Oncology
- Hao-Yuan Wang Division of Hematology & Oncology
- Yao-Chung Liu Division of Hematology & Oncology
- 李函叡 Division of Radiology
- Po-Shen Ko Division of Hematology & Oncology
- Chia-Jen Liu Division of Hematology & Oncology
- Ting-An Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Sin-Syue Li Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
- Hung Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Lymphoma, Mantle-Cell
Objectives
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.
Test Drug
LOXO-305
Active Ingredient
LOXO-305
Dosage Form
Tablet
Dosage
25mg and 100mg
Endpoints
Primary Outcome Measures :
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) [ Time Frame: Up to approximately 24 months ]
Assessed per Lugano criteria
Secondary Outcome Measures :
To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: 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 [ Time Frame: Up to approximately 24 months ]
Time from randomization to time when discontinuation criteria met
Time to worsening (TTW) of MCL-related symptoms [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 24 months ]
Assessed by survival
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) [ Time Frame: Up to approximately 24 months ]
Assessed per Lugano criteria
Secondary Outcome Measures :
To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: 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 [ Time Frame: Up to approximately 24 months ]
Time from randomization to time when discontinuation criteria met
Time to worsening (TTW) of MCL-related symptoms [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 24 months ]
Assessed by survival
Inclution Criteria
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
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
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
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
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
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
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
500 participants
