Multi-cohort Study to Customize Ibrutinib Treatment Regimens for Patients with Previously Untreated Chronic Lymphocytic Leukemia TAILOR

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Apr 2024 → ongoing

Decision date (initial)

2023-11-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Dose response

To evaluate the efficacy of I+V and ibrutinib monotherapy regimens using a tailored treatment approach in which dosing of ibrutinib is either proactively reduced or reactively modified (per the label) in response to AEs, compared with clinical trial-based historical controls of ibrutinib monotherapy and I+V

Conditions and MedDRA coding

Untreated Chronic Lymphocytic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 2. Diagnosis of CLL/SLL that meets iwCLL diagnostic criteria
2. 3. For I+V cohorts: ECOG performance status of 0-1. For ibrutinib monotherapy cohorts: ECOG performance status of 0-2
3. 4. Active disease meeting at least 1 of the following iwCLL criteria for requiring treatment: a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. b. Massive (ie, ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly. c. Massive nodes (ie, ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. d. Progressive lymphocytosis with an increase of ≥50% over a 2-month period, or LDT <6 months. e. Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids. f. Symptomatic or functional extranodal involvement (eg, 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. Significant fatigue (ie, ECOG performance scale 2 or worse; cannot work or unable to perform usual activities). iii. Fevers ≥100.5°F or 38.0°C for ≥2 weeks without evidence of infection. iv. Night sweats for ≥1 month without evidence of infection.
4. 15. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days (except for pegylated G-CSF [pegfilgrastim] and darbepoetin, which require at least 14 days) prior to screening laboratory assessment defined as: a. ANC >750/μL independent of growth factor support; b. Platelet count >50,000/μL independent of transfusion support for at least 7 days prior to enrollment; c. Hemoglobin >8.0 g/dL independent of transfusion support for >7 days prior to enrollment
5. 16. Adequate hepatic function, defined as: a. Serum AST or ALT ≤3.0×ULN; b. Bilirubin ≤1.5×ULN (unless bilirubin rise is due to congenital nonhemolytic hyperbilirubinemias or of non-hepatic origin); c. Prothrombin time/international normal ratio <1.5×ULN and activated partial thromboplastin time <1.5×ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder)
6. 17. Adequate renal function, defined as follows (using the Cockcroft-Gault equation): a. For I+V cohorts: i. In participants aged <75 years at enrollment, CrCl ≥45 mL/min; ii. In participants aged ≥75 years at enrollment, CrCl ≥60 mL/min. b. For ibrutinib monotherapy cohorts, CrCl ≥45 mL/min

Exclusion criteria 5

1. 1. Medical history of: a. Other malignancies, except: i. Any malignancy that was not progressing nor requiring treatment change in the last 12 months. ii. Malignancies treated within the last 12 months and considered at very low risk for recurrence: 1. Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS). 2. Skin cancer (non-melanoma or melanoma). 3. Non-invasive cervical cancer. 4. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents. 5. Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment). iii. Other malignancy that is considered at minimal risk of recurrence. b. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as those participants with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study treatment, or the need for prednisone >20 mg daily (or corticosteroid equivalent) to treat or control the autoimmune disease. c. Recent infection requiring systemic treatment that is ongoing or was completed ≤14 days before the first dose of study treatment, or any uncontrolled active systemic infection. d. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia). e. Stroke or intracranial hemorrhage within 6 months prior to enrollment. f. Difficult to control hypertension (defined as requiring ≥3 hypertensive medications) or screening systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg. For participants whose screening blood pressure exceeds a systolic blood pressure of 160 mmHg or a diastolic blood pressure of 100 mmHg, the investigator should review and manage the participant appropriately according to individual practice. The participant may be rescreened if it can be demonstrated that the blood pressure reading was a single isolated elevation or is subsequently controlled and stable. g. History of myocardial infarction, ventricular arrhythmia, unstable angina, or acute coronary syndrome within 12 months prior to enrollment (if >1 year, cardiology consultation is recommended prior to study enrollment)
2. 2. Known or suspected Richter’s transformation or CNS involvement
3. 5. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class II, III, or IV congestive heart failure as defined by the New York Heart Association Functional Classification (see Section 10.8). For participants who in the investigator’s opinion are considered to have a significant cardiac risk at baseline, the investigator should consider pursuing a cardiology evaluation before screening. It is the investigator’s responsibility to assess the risks and benefits of subsequent study enrolment
4. 10. Participant received prior systemic anticancer therapy (including but not limited to chemotherapy, targeted therapy, immunomodulating therapy, radiotherapy, and/or monoclonal antibody) for treatment of CLL or SLL
5. 20. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise their wellbeing) or that could prevent, limit, or confound the protocol-specified assessments

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best ORR by investigator assessment

Investigational products

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

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 7

Locations

6 EU/EEA countries · 41 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 99 files

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

Application history

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