Ibrutinib and Obinutuzumab as first-line treatment for patients with Chronic Lymphocytic Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2021 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514824-18-00

EudraCT number

2021-000311-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Evaluate the percentage of BM MRD <10-4 in BM at +30 days of follow-up after ibrutinib (Cycles 1-24) and obinutuzumab (Cycle 13 Days 1,2,8,15; Cycles 14-18 Day 1)

Conditions and MedDRA coding

chronic lymphocytic leukemia/small lymphocytic lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age >=18 years
2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocyte lymphoma (SLL) according to iwCLL diagnostic criteria
3. Previously untreated active disease requiring treatment according to iwCLL criteria
4. ECOG PS 0 or 1
5. Lymph node disease measurable (longest diameter> 1.5 cm) by CT
6. Adequate blood count defined as: Absolute neutrophil count (ANC)> 750 cells / μL (750 cells / mm3 or 0.75 x 109 / L), Platelet count> 30,000 / μL (30,000 cells / mm3 or 30 x 109 / L), Hemoglobin> 8.0 g / dL
7. Adequate liver and kidney function defined as: Serum aspartate transaminase (AST) or alanine transaminase (ALT) =3.0 x upper limit of normal (ULN) , Estimated Creatinine Clearance (CrCl) =30 mL / min (Cockcroft-Gault), Bilirubin =1.5 x ULN (unless increased bilirubin is due to Gilbert's syndrome or of non-hepatic origin)
8. Prothrombin time (PT) / International normal ratio (INR) <1.5 x ULN and PTT (activated partial thromboplastin time [aPTT]) <1.5 x ULN (unless abnormalities are related to coagulopathy or bleeding disorder)

Exclusion criteria 11

1. Any prior therapy (including but not limited to chemotherapy, targeted therapy, immunomodulatory therapy, radiotherapy, and / or monoclonal antibody) used to treat CLL or SLL.
2. Patients with del (17p) and / or TP53 mutation according to centralized laboratory assessment.
3. History of other malignancies, except: Malignant tumor treated with curative intent and with no known active disease present for =3 prior to first dose of study drug and deemed low risk of recurrence by treating physician, Malignant skin neoplasm not adequately treated or lentigo maligna with no evidence of disease, Adequately treated carcinoma in situ with no evidence of disease.
4. Known or suspected history of Richter's transformation.
5. Known hypersensitivity to one or more study drugs.
6. Known bleeding disorders (eg von Willebrand disease or haemophilia).
7. History of stroke or intracranial haemorrhage within 6 months prior to enrollment.
8. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection. Individuals who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who test positive for PCR will be excluded.
9. Inability to swallow capsules / tablets or malabsorption syndrome, any disease that significantly affects gastrointestinal function, or resection of the stomach or small intestine, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
10. Concomitant use of warfarin or other vitamin K antagonists.
11. Major surgery within 4 weeks of the first dose of study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with MRD <10-4 in BM at +30 follow-up days after completion of therapy

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Paolo Ghia

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Paolo Ghia

Locations

1 EU/EEA country · 6 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 5 files

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

Application history

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