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Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With CLL or SLL

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ClinicalTrials.gov Identifier: NCT04666038
Recruitment Status : Recruiting
First Posted : December 14, 2020
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information
First Submitted Date  ICMJE December 7, 2020
First Posted Date  ICMJE December 14, 2020
Last Update Posted Date April 5, 2021
Actual Study Start Date  ICMJE March 9, 2021
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2020)
To evaluate progression-free survival (PFS) of LOXO-305 monotherapy (Arm A) compared to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B) [ Time Frame: Up to approximately 36 months ]
Assessed per iwCLL 2018
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2021)
  • To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR) [ Time Frame: Up to approximately 36 months ]
    Assessed per iwCLL 2018
  • To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    Assessed by survival
  • To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 36 months ]
    Defined as time from randomization to next systemic anticancer therapy for CLL/SLL
  • Time to worsening (TTW) of CLL/SLL related symptoms [ Time Frame: Up to approximately 36 months ]
    Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms
  • Time to worsening (TTW) of physical function [ Time Frame: Up to approximately 36 months ]
    Using the 5 physical function items identified from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) questionnaire (also known as the EORTC IL 19 questionnaire), physical function will be measured. The range of raw scores for these items could be from 0-20 with the highest score indicating worst function.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2020)
  • To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR) [ Time Frame: Up to approximately 36 months ]
    Assessed per iwCLL 2018
  • To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    Assessed by survival
  • To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 36 months ]
    Defined as time from randomization to next non-protocol-specified therapy for CLL/SLL
  • Time to worsening (TTW) of CLL/SLL related symptoms [ Time Frame: Up to approximately 36 months ]
    Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms
  • Time to worsening (TTW) of physical function [ Time Frame: Up to approximately 36 months ]
    Using the 5 physical function items identified from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) questionnaire (also known as the EORTC IL 19 questionnaire), physical function will be measured. The range of raw scores for these items could be from 0-20 with the highest score indicating worst function.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With CLL or SLL
Official Title  ICMJE A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)
Brief Summary This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four 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 either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A and Arm B.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Eligible patients will be randomized in 1:1 into Arm A or Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Intervention  ICMJE
  • Drug: LOXO-305
    Oral LOXO-305
    Other Name: Pirtobrutinib
  • Drug: Idelalisib
    Oral
    Other Name: Zydelig
  • Drug: Bendamustine
    IV
    Other Name: Treanda, Treakisym, Ribomustin, Levact
  • Drug: Rituximab
    IV
    Other Name: Rituxan, MabThera, Truxima
Study Arms  ICMJE
  • Experimental: Arm A (LOXO-305)
    Orally
    Intervention: Drug: LOXO-305
  • Active Comparator: Arm B (Idelalisib plus rituximab [IdelaR] or bendamustine plus rituximab [BR])
    Investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).
    Interventions:
    • Drug: Idelalisib
    • Drug: Bendamustine
    • Drug: Rituximab
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 7, 2020)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria
  • Previously treated with a covalent BTK inhibitor
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support
  • Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 14 days of Cycle 1 Day 1
  • Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 14 days of C1D1. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ (75 × 109/L).
  • AST and ALT ≤ 3.0 x upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 x ULN.
  • Estimated creatinine clearance of ≥ 30 mL/min.

Exclusion Criteria:

  • Known or suspected Richter's transformation at any time preceding enrollment.
  • Known or suspected history of central nervous system (CNS) involvement by CLL/SLL
  • Ongoing drug-induced liver injury
  • Active uncontrolled auto-immune cytopenia
  • Significant cardiovascular disease
  • History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days
  • Active hepatitis B or hepatitis C
  • Known active cytomegalovirus (CMV) infection.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
  • Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.
  • Clinically significant active malabsorption syndrome or inflammatory bowel disease
  • Prior exposure to non-covalent (reversible) BTK inhibitor.
  • Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
  • Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers and/or strong P-glycoprotein (P-gp) inhibitors
  • Vaccination with a live vaccine within 28 days prior to randomization
  • Patients with the following hypersensitivity:

    1. Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305, idelalisib, and bendamustine
    2. Prior significant hypersensitivity to rituximab
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04666038
Other Study ID Numbers  ICMJE LOXO-BTK-20020
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 Not Provided
Responsible Party Eli Lilly and Company ( Loxo Oncology, Inc. )
Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Safi Shahda, MD Loxo Oncology
PRS Account Eli Lilly and Company
Verification Date April 2021

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