A Phase 3 Study Comparing Pirtobrutinib to Ibrutinib in CLL/S

Phase 1

• Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-003206-41-PT
• Lead Sponsor: oxo Oncology, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-26
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 650

Inclusion Criteria

Patients are eligible to be included in the study only if all of the following criteria apply:
Age
1. Age 18 years or older per local regulations at time of enrollment.
Type of Patient and Disease Characteristics
2. Confirmed diagnosis by redacted local laboratory report of CLL/SLL, as defined by iwCLL 2018 criteria, and to include the following:
a) B-cells co-expressing the surface antigen CD5 together with at least one B-cell antigen (CD19, CD20, CD23) and either ? or ? light -chain restricted
b) = 5 × 109 B lymphocytes/L (5000/µL) in the peripheral blood. For SLL patients, history of < 5 × 109 B lymphocytes/L (5000/µL) in the peripheral blood is allowed
c) Prolymphocytes may comprise = 55% of blood lymphocytes
3. A requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy such that at least 1 of the following should be met:
a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (such as hemoglobin < 10 g/dL) and/or thrombocytopenia (such as platelets = 100 × 109/L)
b) Massive (i.e., spleen edge = 6 cm below the left costal margin) or progressive or symptomatic splenomegaly (> 13 cm)
c) Massive nodes (i.e., = 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
d) Progressive lymphocytosis with an increase of > 50% over a 2-month period or lymphocyte doubling time < 6 months. Factors contributing to lymphocytosis other than CLL/SLL (e.g., infections, steroid administration) should be excluded
e) Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids
f) Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine)
g) Disease-related symptoms as defined by any of the following:
i) Unintentional weight loss = 10% within the previous 6 months
ii) Fevers = 100.5°F or 38.0°C for 2 or more weeks without evidence of infection
iii) Night sweats for = 1 month without evidence of infection
4. Known 17p deletion status (wildtype or deleted)
5. ECOG 0 to 2.
6. Must have adequate organ function, as defined per protocol. These values must be met during the Screening Period as well as predose on C1D1.
7. Patients are required to have had the following washout periods prior to planned C1D1:
a) Targeted agents or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is greater
b) Therapeutic monoclonal antibodies: 4 weeks
c) Palliative limited field radiation: 7 days
d) Broad field radiation (= 30% of bone marrow or whole brain radiotherapy): 28 days
8. Prior treatment related AEs must have recovered to Grade = 1, pretreatment baseline, or are controlled with medications without meeting other exclusion criteria (with the exception of alopecia).
Contraception
9. Willingness of men and WOCBP, and their partners, to observe barrier and highly effective birth control methods as outlined in Section 10.2 (and below) for the duration of treatment and for 6 months following the last dose of study treatment.
Highly effective birth control methods with a failure rate of less than 1% per year when used consistently and correctly are recommended (CTFG 2020):
a. Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally
b. Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant
c. IUD
d. IUS
e. Bilateral tubal occlusion
f. Vasectomized partner
g.

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Known or suspected Richter’s transformation to DLBCL, prolymphocytic leukemia, or Hodgkin’s lymphoma at any time preceding enrollment
2. Known or suspected history of CNS involvement by CLL/SLL
3. Previous or concurrent cancer distinct from CLL/SLL within 3 years prior to randomization; patients with prior cancers may be enrolled with documented Sponsor approval, examples include:
a) Curatively treated nonmelanomatous skin cancer or lentigo maligna melanoma
b) Curatively treated cervical carcinoma in situ
c) Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years (may be receiving adjuvant hormonal therapy)
d) Localized prostate cancer undergoing active surveillance
4. Major surgery within 4 weeks of planned start of study drug
5. A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic, that, in the opinion of the Investigator, would adversely affect the patient’s participation in this study or interpretation of study outcomes
6. Ongoing drug-induced liver injury, primary biliary cirrhosis, and/or extrahepatic obstruction caused by cholelithiasis and/or cirrhosis of the liver
7. History of allogeneic or autologous SCT or CAR-T therapy within the past 60 days
8. Active uncontrolled autoimmune cytopenia (e.g., autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) for at least 4 weeks prior to study enrollment
9. Significant cardiovascular disease defined as any of the following:
a) Unstable angina or acute coronary syndrome within the past 2 months prior to randomization,
b) History of myocardial infarction within 3 months prior to randomization,
c) Documented LVEF by any method of = 40% within the 12 months prior to randomization, unless subsequent measurements (= 2 of any kind, separated by a minimum of 3 weeks) documents LVEF recovery > 40%, and/or
d) = Grade 3 New York Heart Association functional classification system of heart failure, uncontrolled or symptomatic arrhythmias
10. Prolongation of the QTc for heart rate using Fridericia’s Formula (QTcF) > 470 msec on at least 2 of 3 consecutive ECGs, and mean QTcF > 470 msec on all 3 ECGs, during Screening
a) QTcF is calculated using Fridericia’s Formula (QTcF = QT/(RR^0.33)
b) Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities can be attempted at the Investigator’s discretion, and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation or electrolyte supplementation
c) Correction of QTc for underlying bundle branch block permissible
11. Hepatitis B or hepatitis C testing indicating active/ongoing infection based on Screening laboratory tests as defined as:
a) HBV: Patients with positive HBsAg are excluded. Patients with positive anti-HBc and negative HBsAg require hepatitis B PCR evaluation before randomization. Patients who are hepatitis B PCR-positive will be excluded.
b) HCV: Patients with positive hepatitis C antibody are excluded. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C RNA before randomization. Patients who are hepatitis C RNA-positive will be excluded.
12. Known active CMV infection. Patients with negative status are eligible.
13.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified