Single Agent Obinutuzumab in Relapsed/Refractory Post-Transplant Lymphoproliferative Disorder (PTLD)

Study Overview
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Brief Summary
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Patients with post transplant lymphoproliferative disorder (PTLD) that have been treated with at least one type of chemotherapy, but whose lymphoma is not responding or coming back after the previous treatment will be asked to participate in this study. This clinical trial uses a drug called Obinutuzumab. The Food and Drug Administration (FDA) has approved Obinutuzumab for sale in the United States for certain diseases. Obinutuzumab is still being studied in clinical trials to learn more about what its side effects are and whether or not it is effective in the disease or condition being studied. Obinutuzumab is considered an investigational drug in this study Obinutuzumab (GA101) is an antibody directed against cluster of differentiation antigen 20 (CD20). Antibodies are protein that are part of the immune system that can target cancer cells. Obinutuzumab sticks to a target called CD20. CD20 is an important molecule on some cancer cells (including non-Hodgkin lymphoma) and some normal cells of the immune system. This study is being done to test if the study drug has an effect on post transplant lymphoproliferative disorder and to see how lymphoma will respond to the study drug.

Detailed Description
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Primary Objective: • To determine the overall response rate of obinutuzumab in relapsed/refractory post-transplant lymphoproliferative disorder (PTLD) in both solid organ transplant (SOT) and bone marrow transplant (BMT) patients Secondary Objectives: Complete remission (CR) rate Duration of response (DOR) Progression free survival (PFS) Overall survival (OS) Time to treatment failure (TTF) Safety and tolerability of obinutuzumab Patient Population: Relapsed or refractory post-transplant lymphoproliferative disorder (PTLD) patients who have received at least one prior therapy Study Design: Phase II study of single agent obinutuzumab in relapsed/refractory (RR) post-transplant lymphoproliferative disorder (PTLD) in both SOT and BMT patients

Official Title
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Phase II Study of Single Agent Obinutuzumab in Relapsed/Refractory Post-Transplant Lymphoproliferative Disorder (PTLD)

Conditions
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Post-transplant Lymphoproliferative Disorder, PTLD

Intervention / Treatment
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* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed relapsed/refractory post-transplant lymphoproliferative disorder Relapsed/refractory disease with at least 1 prior chemotherapy regimen Measurable disease ≥1.5 cm Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. ECOG 3 will be permitted if the decline in the performance status is attributed to the lymphoma Able to sign the consent form Adequate organ function bilirubin ≤1.5 times upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN or ≤5 times ULN for patients with document hepatic involvement with lymphoma serum creatinine clearance >50 ml/min absolute neutrophil count (ANC) ≥500/μL (unless documented bone marrow involvement with lymphoma) hemoglobin >8 gm/dl platelet count ≥50,000/μL (unless documented bone marrow involvement with lymphoma) Exclusion Criteria: Prior treatment with obinutuzumab Pregnancy or breast feeding women Current active malignancy other than PTLD, requiring active treatment Presence of central nervous system (CNS) involvement HIV positive patients Myocardial infarction within the past 6 months Patients with the following medical conditions that could affect their participation in the study: any active acute or chronic or uncontrolled infection liver disease including history of viral hepatitis B or C, evidence of cirrhosis, chronic active or persistent hepatitis a known history of HIV symptomatic cardiac disease, including congestive heart failure, coronary artery disease, and arrhythmias Current therapy with chemotherapy or investigational agents within 4 weeks of start of study treatment

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obinutuzumab<br>Patients will be treated with a total of 2 cycles of obinutuzumab. | Drug: Obinutuzumab<br>* Patients will be treated with a total of 2 cycles of obinutuzumab. Cycle 1 obinutuzumab dose is 1000 mg given intravenously (IV) on day 1, 8, 15. Cycle #1 day #1 dose of 1000 mg of obinutuzumab will be administered over 2 days. During Cycle 1, Day 1, 100 mg will be administered. On the following day (Cycle 1, Day 2), 900 mg will be administered. During cycle 2 patients will receive a single dose of obinutuzumab1000 mg IV on day 1. Cycle #2 will be given 21 days after the first cycle.<br>* Other names: Gazyva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate will be estimated by the total number of patients who achieve a CR and PR divided by the total number of evaluable patients. Response will be assessed using CT scans according to the revised Cheson criteria CR is defined as complete resolution of all clinically detectable disease and disease related symptoms that were present prior to therapy PR is defined as at least 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses | Up to 36 months after beginning treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | CR is defined as complete resolution of all clinically detectable disease and disease related symptoms that were present prior to therapy. A post-treatment residual mass of any size is permitted as long as it is proton emission tomography (PET) negative. CR rate will be calculated by dividing the dividing the total number of patients who have achieved CR by the total number of patients who have achieved a CR and PR. | Up to 36 months after beginning treatment | 
| Progression Free Survival | Progression-free survival (PFS) is defined as the time from enrollment into the study to disease progression or death due to any cause. It may be defined as the date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. | Up to 36 months after beginning treatment | 
| Overall Survival | The OS is defined as the time from enrollment to the time of death due to any cause. For a patient who is alive at the end of study follow-up, observation of OS is censored on the date of last contact. | Up to 36 months after beginning treatment | 
| Duration of Response | Duration of response (DOR) is defined as the time from first documentation of objective tumor response (CR or PR) to the time to tumor progression or death due to any cause. | Up to 36 months after beginning treatment | 
| Time to Treatment Failure | Time to treatment failure (TTF) is defined as the time from enrollment to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. | Up to 36 months after beginning treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed, refractory