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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. )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: LOXO-305 Drug: Idelalisib Drug: Bendamustine Drug: Rituximab Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
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
Official Title: 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)
Actual Study Start Date : March 9, 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A (LOXO-305)
Orally
 Drug: LOXO-305
Oral LOXO-305
Other Name: Pirtobrutinib
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).
 Drug: Idelalisib
Oral
Other Name: Zydelig

Drug: Bendamustine
IV
Other Name: Treanda, Treakisym, Ribomustin, Levact

Drug: Rituximab
IV
Other Name: Rituxan, MabThera, Truxima


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.


Eligibility Criteria
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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 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
Contacts and Locations
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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): NCT04666038


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

Locations
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United States, Arizona
Palo Verde Hematology Oncology, LTD Recruiting
Glendale, Arizona, United States, 85304
United States, Oregon
Willamette Valley Cancer Institute and Research Center Recruiting
Eugene, Oregon, United States, 97401
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
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Study Director: Safi Shahda, MD Loxo Oncology
More Information
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Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04666038    
Other Study ID Numbers: LOXO-BTK-20020
First Posted: December 14, 2020    Key Record Dates
Last Update Posted: April 5, 2021
Last Verified: April 2021

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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. ):
Hematologic Disease
Lymphoma, non-Hodgkin's
Lymphoma, B-cell
Lymphoma
Bruton's tyrosine kinase inhibitor
 Ibrutinib
Acalabrutinib
Zanubrutinib
Pirtobrutinib
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
 Bendamustine Hydrochloride
Idelalisib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors