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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Loxo Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Jul 2021 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Loxo Oncology Inc., a wholly owned subsidiary of Eli Lilly and Company

External identifiers

EU CT number

2023-507697-40-00

EudraCT number

2020-004554-30

ClinicalTrials.gov

NCT04666038

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate progression free survival (PFS) of pirtobrutinib as monotherapy (Arm A) compared to investigator's choice of idelalisib plus Rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B).

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age 18 or older per local regulations at time of enrollment.
2. Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria
3. Previously treated with a covalent BTK inhibitor
4. Eastern Cooperative Oncology Group (ECOG) 0 2
5. Absolute neutrophil count ≥ 0.75 × 10^9/L without granulocyte colony stimulating factor support, or ≥ 0.50 × 10^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte colony stimulating factor support is permitted in patients with documented bone marrow involvement
6. Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement
7. Platelets ≥ 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x 10^9/L are excluded
8. AST and ALT ≤ 3.0 x upper limit of normal (ULN)
9. Total bilirubin ≤ 1.5 x ULN
10. Estimated creatinine clearance of ≥ 30 mL/min
11. Willing and capable of giving signed informed consent as described in Section 10.1.2 Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 16

1. Known or suspected Richter's transformation at any time preceding enrollment
2. Known or suspected history of central nervous system (CNS) involvement by CLL/SLL
3. Ongoing drug induced liver injury
4. Active uncontrolled auto immune cytopenia
5. Significant cardiovascular disease
6. History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor modified T cells (CAR T) therapy within the past 60 days
7. Active hepatitis B or hepatitis C
8. Known active cytomegalovirus (CMV) infection
9. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
10. Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count
11. Clinically significant active malabsorption syndrome or inflammatory bowel disease
12. Prior exposure to non covalent (reversible) BTK inhibitor
13. Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
14. Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers
15. Vaccination with a live vaccine within 28 days prior to randomization
16. Patients with the following hypersensitivity: 1. Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine. Prior significant hypersensitivity to rituximab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Assessed by Independent Review Committee (IRC): • PFS per iwCLL 2018

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Loxo Oncology Inc.

Sponsor organisation

Loxo Oncology Inc.

Address

281 Tresser Boulevard Floor 9th

City

Stamford

Postcode

06901-3238

Country

United States

Scientific contact point

Organisation

Loxo Oncology Inc.

Contact name

Eli Lilly & Co

Public contact point

Organisation

Loxo Oncology Inc.

Contact name

Eli Lilly & Co

Third parties 10

Locations

11 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 166 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications