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A Study to Evaluate Efficacy & Safety of Obinutuzumab, Ibrutinib, and Venetoclax in Richter's Syndrome;

NCT04939363 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 12

Last updated 2024-12-10

No results posted yet for this study

Summary

Richter's syndrome (RS) is a life-threatening complication of chronic lymphocytic leukemia (CLL). It is associated with a switch in histopathology and biology, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL). The development of RS is accompanied by the onset of B symptoms, rapid growth of lymphadenopathy, extra-nodal disease, significant elevations of lactate dehydrogenase (LDH), and associated multi-organ dysfunction from invasive or obstructive processes RS occurs in 2-10% of CLL patients with an incidence rate of 0.5% per year. The molecular pathogenesis of RS involves inactivation of the tumor protein p53 (TP53) tumor suppressor gene in 50-60% of cases and activating aberrations of NOTCH1 and myelocytomatosis oncogene (MYC) in about 30% of cases. .

These distinct molecular footprints of RS are chemoresistance leading to an aggressive clinical course with low response rates and poor outcomes.Taking into consideration that in addition to the underlying aggressive disease, most RS patients are often at an advanced age and suffer from numerous other comorbidities. Additionally, intensive chemotherapy regimens are highly toxic to this population group and lead to excessive treatment-related morbidity. Enrolling DLBCL-RS patients in clinical trials is therefore justifiable, particularly those with RS that is clonally related to the predisposed underlining CLL disease. Due to the poor activity of immunochemotherapy, the possibility of using novel agents in the treatment of RS is of great interest.

The toxicity and the efficacy of the combination of cluster of anti differentiation antigen 20 (anti-CD20) antibody (e.g. Obinutuzumab or Rituximab) with Ibrutinib and/or Venetoclax have been already reported in both relapsed and naïve patients with CLL. The use of these three agents in combination is highly active in CLL and has manageable side effects. In addition, recent reports showed that treatment with Ibrutinib or Venetoclax as a single drug are active in RS.

Herein the investigators propose a phase 2, open-label, non-randomized, single arm, multi-center study aiming to assess the safety and efficacy with the combination of Ibrutinib, Venetoclax and Obinutuzumab in patients with RS

.

Conditions

  • Richter's Syndrome

Interventions

COMBINATION_PRODUCT

Obinutuzumab with Ibrutinib and Venetoclax

1. Obinutuzumab intravenous infusion: 2. Ibrutinib PO 560mg daily starting on cycle 1 day 1 for 12 cycles. 3. Venetoclax with an accelerated ramp-up and close inpatient Tumor Lysis Syndromes (TLS) monitoring starts on cycle 1 day 15 to the target dose of 400mg daily for a total of 12 cycles:

Sponsors & Collaborators

  • Tel-Aviv Sourasky Medical Center

    collaborator OTHER_GOV

  • Bnai Zion Medical Center

    lead OTHER_GOV

Principal Investigators

  • Yair Herishanu, Prof · TASMC

  • Tamar Tadmor, Prof · Bnai Zion Medical Center

  • Ohad Benjamini, Dr. · Sheba Medical Center

  • Neta Goldschmidt, Prof · Hadassah Medical Organization

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-08-08
Primary Completion
2024-10-09
Completion
2024-12-04

Countries

  • Israel

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04939363 on ClinicalTrials.gov