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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Richter Syndrome

Intervention / Treatment
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* Drug: Obinutuzumab
* Drug: Ibrutinib
* Other: CHOP


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel assignment based on fitness of participants
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fit arm<br>ibrutinib and obinutuzumab in combination with the CHOP regimen | Drug: Obinutuzumab<br>* 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<br>* Other names: gazyva;Drug: Ibrutinib<br>* 560mg po daily<br>* Other names: imbruvica;Other: CHOP<br>* cyclophosphamide, doxorubicin, vincristine, and prednisone<br>* Other names: CHOP Regimen;|
| Experimental: Frail arm<br>ibrutinib and obinutuzumab | Drug: Obinutuzumab<br>* 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<br>* Other names: gazyva;Drug: Ibrutinib<br>* 560mg po daily<br>* Other names: imbruvica;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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richter, leukemia