search
Back to results

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

Primary Purpose

Post-transplant Lymphoproliferative Disorder, PTLD

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Obinutuzumab
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-transplant Lymphoproliferative Disorder focused on measuring relapsed, refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Obinutuzumab

    Arm Description

    Patients will be treated with a total of 2 cycles of obinutuzumab.

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    March 16, 2017
    Last Updated
    March 16, 2017
    Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    Genentech, Inc.
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03086395
    Brief Title
    Single Agent Obinutuzumab in Relapsed/Refractory Post-Transplant Lymphoproliferative Disorder (PTLD)
    Official Title
    Phase II Study of Single Agent Obinutuzumab in Relapsed/Refractory Post-Transplant Lymphoproliferative Disorder (PTLD)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Funding Unavailable
    Study Start Date
    April 1, 2017 (Anticipated)
    Primary Completion Date
    January 1, 2018 (Anticipated)
    Study Completion Date
    January 1, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    Genentech, Inc.

    4. Oversight

    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.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Post-transplant Lymphoproliferative Disorder, PTLD
    Keywords
    relapsed, refractory

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Obinutuzumab
    Arm Type
    Experimental
    Arm Description
    Patients will be treated with a total of 2 cycles of obinutuzumab.
    Intervention Type
    Drug
    Intervention Name(s)
    Obinutuzumab
    Other Intervention Name(s)
    Gazyva
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Overall Response Rate
    Description
    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
    Time Frame
    Up to 36 months after beginning treatment
    Secondary Outcome Measure Information:
    Title
    Complete Response Rate
    Description
    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.
    Time Frame
    Up to 36 months after beginning treatment
    Title
    Progression Free Survival
    Description
    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.
    Time Frame
    Up to 36 months after beginning treatment
    Title
    Overall Survival
    Description
    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.
    Time Frame
    Up to 36 months after beginning treatment
    Title
    Duration of Response
    Description
    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.
    Time Frame
    Up to 36 months after beginning treatment
    Title
    Time to Treatment Failure
    Description
    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.
    Time Frame
    Up to 36 months after beginning treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Deepa Jagadeesh, MD, MPH
    Organizational Affiliation
    Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs