Ibrutinib for the Treatment of AIHA in Patients With CLL/SLL or CLL-like MBL

Ibrutinib for the Treatment of Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or CLL-like Monoclonal B-cell Lymphocytosis

This is a multicenter, single arm, phase II study aimed at evaluating ibrutinib therapy for the treatment of AIHA in patients with CLL/SLL or CLL-like MBL.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Autoimmune Hemolytic Anemia; Monoclonal B-Cell Lymphocytosis CLL-Type
• Intervention / Treatment: Drug: Ibrutinib 420 mg

Detailed Description

This is a multicenter, phase II study to assess the efficacy of ibrutinib for the treatment of AIHA in adult patients with CLL/SLL or CLL-like MBL.

Patients will receive ibrutinib 420 mg/day PO for up to 12 cycles of 28 days in the absence of CLL progression or unacceptable toxicity. Every patient will be followed-up for 1 year after the completion of study treatment.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paola Fazi; Phone Number: 0670390528; Email: p.fazi@gimema.it
• Study Contact Backup: Name: Enrico Crea; Phone Number: 0670390514; Email: e.crea@gimema.it

Study Locations

• Italy
  • Firenze, Italy
    • Recruiting
    • Ematologia Osp Careggi
    • Contact: Alessandro Sanna
  • Novara, Italy
    • Recruiting
    • Ematologia Osp Maggiore della Carità
    • Contact: Riccardo Moia
  • Torino, Italy
    • Recruiting
    • Ematologia Osp Molinette
    • Contact: Marta Coscia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of CLL/small lymphocytic lymphoma (SLL) or CLL-like monoclonal B-cell lymphocytosis (MBL) according to IWCLL guidelines.
2. Patients >18 years old
3. Active AIHA (wAIHA or CAD) that i) is relapsed after previous treatment with corticosteroids (with or without rituximab), or ii) is steroid-resistant (failure to obtain hematologic response within 3 weeks on at least 1 mg/kg predniso(lo)ne), or iii) is steroid-dependent (need to continue on predniso(lo)ne at a dose of >10 mg/day to maintain a response). AIHA is defined as: anemia (hemoglobin ≤10 g/dL; or hemoglobin >10 g/dL dependent on transfusions to maintain this level of hemoglobin) and laboratory evidence of hemolysis (presence of 3 of 4 markers: increased reticulocyte count, increased indirect bilirubin, increased lactate dehydrogenase, decreased haptoglobin) and positive DAT (either IgG DAT, C3 DAT or both).
4. Eligibility of patients with DAT-negative active AIHA should be confirmed by the Principal Investigator and co-Principal Investigator for the trial.
5. Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion Criteria:

1. Contraindication to ibrutinib therapy as per treating physician's discretion.
2. Contraindication to ibrutinib therapy as per ibrutinib data sheet (severe hepatic impairment, known allergy to the drug or to one of the excipients, concomitant treatment with warfarin or other vitamin K antagonists).
3. Previous exposure to ibrutinib as CLL-directed therapy.
4. Other CLL/SLL- or AIHA-directed treatment at the time of enrollment in the study, other than corticosteroids.
5. Female patients who are currently in pregnancy or are willing to be pregnant or are lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibrutinib; Patients will receive ibrutinib 420 mg/day orally for up to 12 cycles of 28 days.	Drug: Ibrutinib 420 mg; Patients will receive ibrutinib orally on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of CLL progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ibrutinib efficacy in terms of Overall response rate	Evaluation of the efficacy of ibrutinib therapy for the treatment of AIHA in patients with CLL/SLL or CLL-like MBL in terms of percentage of patients who achieved response (CR + PR)	at month 6

Collaborators and Investigators

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Autoimmune Diseases; Disease Attributes; Hematologic Diseases; Leukocyte Disorders; Leukemia, B-Cell; Chronic Disease; Leukocytosis; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Lymphocytosis
• Other Study ID Numbers: CLL2323

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No