Study of Ibrutinib & Obinutuzumab With/Without CHOP for Richter's Transformation or Richter's Syndrome Patients

Two-arm Phase II Trial Exploring the Use of the Targeted Agents Ibrutinib and Obinutuzumab for the Treatment of Patients With a Diagnosis of Richter's Transformation (RT) or Richter's Syndrome (RS)

This research study studies the combination of ibrutinib and obinutuzumab with or without the standard chemotherapy regimen of CHOP to see how well these drugs work in treating patients with a diagnosis of Richter's Transformation or Richter's Syndrome. The Bruton's Tyrosine Kinase (BTK) inhibitor, ibrutinib, may stop growth of cancer cells by blocking the signal needed for cell growth. The monoclonal antibody obinutuzumab may block cancer growth by targeting cells present in Richter's Transformation. Giving ibrutinib with obinutuzumab may be a better treatment for patients with Richter's Transformation. Depending on fitness, the patients may receive ibrutinib and obinutuzumab in combination with a regimen known as CHOP (C= cyclophosphamide, H= hydroxydaunorubicin (also called doxorubicin), O= oncovin (also called vincristine, and P= prednisolone or prednisone (corticosteroids).

Study Overview

• Status: Terminated
• Conditions: Richter Syndrome
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Ibrutinib; Other: CHOP

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health/CLL Research and Treatment Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• confirmed Richter's transformation in treatment naïve and previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma patients
• may have had prior exposure to ibrutinib and other B-cell signaling receptor agents
• Adequate hematologic function
• Adequate liver and kidney function
• Willing and able to participate in all required evaluations and procedures in this study protocol
• Female subjects of childbearing potential must not be pregnant upon study entry
• Male and female subjects who agree to use highly effective methods of birth control

Exclusion Criteria:

• known allergy to any of medications
• chemotherapy taken within 21 days of study treatment
• targeted therapy within 10 days of study treatment
• BCR inhibitors within 24 hours of study treatment
• major surgery within 4 weeks of first dose of study treatment
• women who are pregnant
• known infection with HIV or Hepatitis C
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fit arm; ibrutinib and obinutuzumab in combination with the CHOP regimen	Drug: Obinutuzumab; 100 mg on day 1 and 900 mg on day 2 Cycle 1, 1000 mg on day 8 and 15 of Cycle 1, and 1000 mg on day 1 of Cycles 2-6; Other Names: gazyva; Drug: Ibrutinib; 560mg po daily; Other Names: imbruvica; Other: CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone; Other Names: CHOP Regimen
Experimental: Frail arm; ibrutinib and obinutuzumab	Drug: Obinutuzumab; 100 mg on day 1 and 900 mg on day 2 Cycle 1, 1000 mg on day 8 and 15 of Cycle 1, and 1000 mg on day 1 of Cycles 2-6; Other Names: gazyva; Drug: Ibrutinib; 560mg po daily; Other Names: imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR in subjects treated with combination of ibrutinib and obinutuzumab (with or without CHOP)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Improved Hemoglobin and Platelet Counts.	hematologic improvement	6 months
Progression Free Survival (PFS)	time to progression post treatment of condition	6 months
To Evaluate Patient-reported Outcome (PRO) of Health-related Quality of Life by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACiT-Fatigue)	health-related quality of life using FACIT Fatigue Scale	1 year

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: Pharmacyclics LLC.
• Investigators: Principal Investigator: Jacqueline Barrientos, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Actual): September 28, 2018
• Study Completion (Actual): September 28, 2018

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: leukemia; richter
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: 16-727

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes