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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 : November 12, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information
First Submitted Date  ICMJE December 4, 2020
First Posted Date  ICMJE December 10, 2020
Last Update Posted Date November 12, 2021
Actual Study Start Date  ICMJE March 5, 2021
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • 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 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
Official Title  ICMJE 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)
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Mantle-Cell
Intervention  ICMJE
  • Drug: LOXO-305
    Oral LOXO-305
    Other Name: pirtobrutinib
  • Drug: Ibrutinib
    Oral
    Other Name: Imbruvica
  • Drug: Acalabrutinib
    Oral
    Other Name: Calquence
  • Drug: Zanubrutinib
    Oral
    Other Name: Brukinsa
Study Arms  ICMJE
  • Experimental: Arm A (LOXO-305)
    Orally
    Intervention: Drug: LOXO-305
  • Active Comparator: Arm B (ibrutinib, acalabrutinib, or zanubrutinib)
    Orally
    Interventions:
    • Drug: Ibrutinib
    • Drug: Acalabrutinib
    • Drug: Zanubrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 4, 2020)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2025
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patient Advocacy 1-855-LOXO-305 clinicaltrials@loxooncology.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Czechia,   France,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Portugal,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Canada,   Israel
 
Administrative Information
NCT Number  ICMJE NCT04662255
Other Study ID Numbers  ICMJE LOXO-BTK-20019
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eli Lilly and Company ( Loxo Oncology, Inc. )
Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jennifer Kherani, MD Loxo Oncology
PRS Account Eli Lilly and Company
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP