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

• ClinicalTrials.gov Identifier: NCT04666038
• Recruitment Status: Not yet recruiting
• First Posted: December 14, 2020
• Last Update Posted: February 12, 2021
• Sponsor: Loxo Oncology, Inc.
• Information provided by (Responsible Party): Loxo Oncology, Inc.

Study Description

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

• 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)
• Estimated Study Start Date: February 2021
• Estimated Primary Completion Date: January 2024
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A (LOXO-305); Orally	Drug: LOXO-305; Oral 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).	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

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

• 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.
• 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

Contacts

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

Sponsors and Collaborators

Loxo Oncology, Inc.

Investigators

• Study Director: Safi Shahda, MD; Loxo Oncology

More Information

• Responsible Party: Loxo Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT04666038
• Other Study ID Numbers: LOXO-BTK-20020
• First Posted: December 14, 2020
• Last Update Posted: February 12, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Loxo Oncology, Inc.:

Hematologic Disease; Lymphoma, non-Hodgkin's; Lymphoma, B-cell; Lymphoma; Bruton's tyrosine kinase inhibitor; Ibrutinib; Acalabrutinib; Zanubrutinib

Additional relevant MeSH terms:

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