Back to resultsPolatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma
Primary Purpose
Diffuse Large B-cell Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Polatuzumab vedotin (PV)
Rituximab
Hyaluronidase
Gemcitabine
Cisplatin
Dexamethasone
GCSF
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring Relapsed, refractory, polatuzumab vedotin, rituximab, gemcitabine, cisplatin
Eligibility Criteria
In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.
Inclusion Criteria:
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Biopsy proven diffuse large B-cell lymphoma (DLBCL) in the first relapse (biopsy can be from initial diagnosis). The study will allow high-grade B cell lymphoma, but not including Burkitt's lymphoma.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- Radiologic evidence of active disease within 28 days of starting trial therapy.
- Only one prior line of therapy.
- Prior cancer treatment must be completed at least 14 days prior to the start of treatment and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or start of treatment.
- Subjects may be eligible or ineligible for autologous stem cell transplant
Exclusion Criteria:
- Known severe, active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment that may put the subject at undue risk as determined by the investigator.
- Subjective hearing loss interfering with daily activities or evidence of greater than mild hearing loss compared to age appropriate normal on screening audiometry are excluded.
- Women who are pregnant or breastfeeding or who intend to become pregnant within a year of the last dose of study treatment.
- Subjects with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drugs are eligible for enrollment in the trial.
- Previous exposure to polatuzumab vedotin.
- History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine.
- Contraindication to gemcitabine or cisplatin, or dexamethasone or similar corticosteroid.
- Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 40%, symptomatic coronary artery disease or symptomatic arrhythmias.
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air.
Sites / Locations
- Lineberger Comprehensive Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
The subjects with diffuse large B-cell lymphoma were relapsed or refractory after the first treatment and receiving the study protocol treatment.
Outcomes
Primary Outcome Measures
Overall response rate (ORR)
ORR is defined as the proportion of subjects who received the study treatment, and achieved complete response (CR) or partial response (PR) by Lugano classification.
Complete Response: Complete metabolic response on Positron emission tomography (PET) image or Target nodes/nodal masses must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease on Computerized Tomography (CT).
Partial Response: Score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size on PET and ≥50% decrease in the sum of the products of diameters (SPD) of up to 6 target measurable nodes and extranodal sites on CT.
Secondary Outcome Measures
Complete response rate (CR)
CR is defined as the proportion of subjects who received the study treatment, achieved complete response (CR) by the Lugano classification.
Progression free survival (PFS)
PFS is defined as the time from the start of study treatment until progression by Lugano classification or death.
Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new fluorodeoxyglucose (FDG) -avid foci consistent with lymphoma at the interim or end-of-treatment assessment on PET, or an individual node/lesion must be abnormal with LDi > 1.5 cm, increase by ≥ 50% from the cross product of the shortest axis perpendicular to LDi (SDi) nadir and an increase in LDi or SDi from nadir: 0.5 cm for lesions ≤ 2 cm, 1.0 cm for lesions > 2 cm.
Overall Survival (OS)
OS is defined as the time from the start of treatment until death from any cause.
Number of participants with adverse events
The number of participants with adverse events will be listed and tabulated by grade to determine the safety and toxicity.
Adverse Events will be graded according to The National Cancer Institute (NCI) of Common Terminology Criteria for Adverse Events (CTCAE) version 5. The scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Full Information
NCT ID
NCT05498220
First Posted
August 9, 2022
Last Updated
June 22, 2023
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05498220
Brief Title
Polatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma
Official Title
A Phase II Trial Evaluating the Efficacy of Polatuzumab Vedotin With Rituximab, Gemcitabine, Dexamethasone, and Cisplatin (PV-RGDP) Chemotherapy for Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 17, 2023 (Actual)
Primary Completion Date
August 2028 (Anticipated)
Study Completion Date
August 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger 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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study aimed to evaluate the efficacy of a novel regimen consisting of polatuzumab vedotin in combination with rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) for the treatment of diffuse large B-cell lymphoma that either came back or did not improve after the treatments (rrDLBCL).
This combination has not been approved by the Food and Drug Administration (FDA) for the treatment of rrDLBCL. Salvage therapy (treatment after standard treatment failed) needs to be improved. Rituximab, gemcitabine, dexamethasone, and cisplatin combination is a standard therapy for rrDLBCL and polatuzumab vedotin (PV) is a novel antibody-drug conjugate targeting CD79b. PV has shown efficacy in the setting of rrDLBCL and can improve the response rates of standard salvage therapy.
This study will focus on subjects in the first relapse (one prior regimen) and will include both subjects who are transplant eligible and those who are transplant ineligible.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
Relapsed, refractory, polatuzumab vedotin, rituximab, gemcitabine, cisplatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
The study will use a Simon two-stage design. In the first stage 27 evaluable subjects will be recruited. If there are at least 13 (≥ 13) subjects with a partial or complete response after 4 cycles, another 17 subjects will be enrolled and treated in the second stage of the trial, for a total of 44 evaluable subjects.
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Arm Description
The subjects with diffuse large B-cell lymphoma were relapsed or refractory after the first treatment and receiving the study protocol treatment.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab vedotin (PV)
Intervention Description
1.8 mg/kg, intravenous, at day 1, in every 21 days
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
375 mg/m2 intravenous, at day 1 or day 2, in every 21 days
Intervention Type
Drug
Intervention Name(s)
Hyaluronidase
Intervention Description
1,400 mg/23,400 units sub-cutaneous, starts at cycle 2, in every 21 days
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1,000 mg/m2 intravenous at day 1 and 8, in every 21 days
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75 mg/m2, intravenous, at day 1, in every 21 days
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
40 mg intravenous at day 1, Per oral days at days 2-4
Intervention Type
Drug
Intervention Name(s)
GCSF
Intervention Description
granulocyte-colony stimulating factor (GCSF )
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR is defined as the proportion of subjects who received the study treatment, and achieved complete response (CR) or partial response (PR) by Lugano classification.
Complete Response: Complete metabolic response on Positron emission tomography (PET) image or Target nodes/nodal masses must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease on Computerized Tomography (CT).
Partial Response: Score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size on PET and ≥50% decrease in the sum of the products of diameters (SPD) of up to 6 target measurable nodes and extranodal sites on CT.
Time Frame
Up to 4 months (End of Treatment)
Secondary Outcome Measure Information:
Title
Complete response rate (CR)
Description
CR is defined as the proportion of subjects who received the study treatment, achieved complete response (CR) by the Lugano classification.
Time Frame
Up to 4 months (End of Treatment)
Title
Progression free survival (PFS)
Description
PFS is defined as the time from the start of study treatment until progression by Lugano classification or death.
Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new fluorodeoxyglucose (FDG) -avid foci consistent with lymphoma at the interim or end-of-treatment assessment on PET, or an individual node/lesion must be abnormal with LDi > 1.5 cm, increase by ≥ 50% from the cross product of the shortest axis perpendicular to LDi (SDi) nadir and an increase in LDi or SDi from nadir: 0.5 cm for lesions ≤ 2 cm, 1.0 cm for lesions > 2 cm.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
OS is defined as the time from the start of treatment until death from any cause.
Time Frame
Up to 2 years
Title
Number of participants with adverse events
Description
The number of participants with adverse events will be listed and tabulated by grade to determine the safety and toxicity.
Adverse Events will be graded according to The National Cancer Institute (NCI) of Common Terminology Criteria for Adverse Events (CTCAE) version 5. The scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.
Inclusion Criteria:
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Biopsy proven diffuse large B-cell lymphoma (DLBCL) in the first relapse (biopsy can be from initial diagnosis). The study will allow high-grade B cell lymphoma, but not including Burkitt's lymphoma.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Radiologic evidence of active disease within 28 days of starting trial therapy.
Only one prior line of therapy.
Prior cancer treatment must be completed at least 14 days prior to the start of treatment and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or start of treatment.
Subjects may be eligible or ineligible for autologous stem cell transplant
Exclusion Criteria:
Known severe, active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment that may put the subject at undue risk as determined by the investigator.
Subjective hearing loss interfering with daily activities or evidence of greater than mild hearing loss compared to age appropriate normal on screening audiometry are excluded.
Women who are pregnant or breastfeeding or who intend to become pregnant within a year of the last dose of study treatment.
Subjects with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drugs are eligible for enrollment in the trial.
Previous exposure to polatuzumab vedotin.
History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine.
Contraindication to gemcitabine or cisplatin, or dexamethasone or similar corticosteroid.
Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 40%, symptomatic coronary artery disease or symptomatic arrhythmias.
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lori Stravers
Phone
919-966-8535
Email
lori_stravers@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Dittus, DO, MPH
Organizational Affiliation
Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lori Stravers
Phone
919-966-4432
Email
lori_stravers@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Christopher Dittus, DO, MPH
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Links:
URL
http://unclineberger.org/patientcare/clinical-trials/clinical-trials
Description
University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials
Learn more about this trial
Polatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma
We'll reach out to this number within 24 hrs