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Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL) (BRUIN-MCL-321)

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ClinicalTrials.gov Identifier: NCT04662255
Recruitment Status : Recruiting
First Posted : December 10, 2020
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company ( Loxo Oncology, Inc. )

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 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.

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle-Cell Drug: LOXO-305 Drug: Ibrutinib Drug: Acalabrutinib Drug: Zanubrutinib Phase 3

Detailed Description:
This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 5, 2021
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Arm A (LOXO-305)
Orally
Drug: LOXO-305
Oral LOXO-305
Other Name: pirtobrutinib

Active Comparator: Arm B (ibrutinib, acalabrutinib, or zanubrutinib)
Orally
Drug: Ibrutinib
Oral
Other Name: Imbruvica

Drug: Acalabrutinib
Oral
Other Name: Calquence

Drug: Zanubrutinib
Oral
Other Name: Brukinsa




Primary Outcome Measures :
  1. To compare progression-free survival (PFS) of LOXO-305 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 :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. To compare Overall Response Rate (ORR) of LOXO-305 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

  6. To compare Duration of Response (DOR) of LOXO-305 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

  7. To compare Overall Survival of LOXO-305 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
  • Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
  • Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
  • Vaccination with live vaccine within 28 days prior to randomization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04662255


Contacts
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Contact: Patient Advocacy 1-855-LOXO-305 clinicaltrials@loxooncology.com

Locations
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Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
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Study Director: Jennifer Kherani, MD Loxo Oncology
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Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04662255    
Other Study ID Numbers: LOXO-BTK-20019
First Posted: December 10, 2020    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company ( Loxo Oncology, Inc. ):
Bruton's Tyrosine Kinase Inhibitor
BTKi
Hematologic Disease
Lymphoma, non-Hodgkin's
Lymphoma, B-Cell
Lymphoma
pirtobrutinib
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Acalabrutinib
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action