Study Stopped
Lack of funding
Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas
A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas
3 other identifiers
interventional
20
1 country
3
Brief Summary
The purpose of this study is to evaluate how safe and effective the combination of two different drugs (brentuximab vedotin and rituximab) is in patients with certain types of lymphoma. This study is for patients who have a type of lymphoma that expresses a tumor marker called CD30 and/or a type that is associated with the Epstein-Barr virus (EBV-related lymphoma) and who have not yet received any treatment for their cancer, except for dose-reduction or discontinuation (stoppage) of medications used to prevent rejection of transplanted organs (for those patients who have undergone transplantation). This study is investigating the combination of brentuximab vedotin and rituximab as a first treatment for lymphoma patients
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2013
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 27, 2013
CompletedFirst Posted
Study publicly available on registry
March 5, 2013
CompletedStudy Start
First participant enrolled
March 5, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 18, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2018
CompletedResults Posted
Study results publicly available
January 5, 2021
CompletedSeptember 1, 2021
August 1, 2021
4.5 years
February 27, 2013
December 9, 2020
August 30, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
For Phase I: The Recommended Phase 2 Dose of Brentuximab Vedotin in Combination With Rituximab.
To identify the recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD) of brentuximab vedotin in combination with rituximab. The dose limiting toxicity monitoring period for brentuximab vedotin and rituximab is first 21 days (during induction).The RP2D/MTD will be defined as the highest dose of brentuximab vedotin that causes dose limiting toxicities (DLTs) in \<2 of 6 patients. The Phase I portion of the study follows a 3+3 design. Brentuximab has two dose levels: Level 1 (starting dose) 1.2 mg/kg IV, and Level -1 (de-escalation dose): 0.8 mg/kg IV. Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
The first 21 days of Induction
Phase 1: Number of Dose Limiting Toxicities of Brentuximab Vedotin and Rituximab in Patients With Immunosuppressed Lymphoid Malignancies.
Dose limiting toxicities (DLT) will be monitored for Phase 1 patients for the first 21 days of Induction (the DLT monitoring period) to evaluate safety. In general, a non-hematologic DLT is defined as any Grade ≥ 3 toxicity, and a hematologic DLT is defined as any Grade ≥ 4 toxicity, both by CTCAE v4.03 criteria.
The first 21 days of induction
Phase II: Percent of Participants With an Overall Response
Overall response will be defined as the detection of Partial Response (PR) or Complete Response (CR) by CT or PET/CT, and/or resolution of marrow-only involvement. Response will be assessed according to the Revised Response Criteria for Malignant Lymphoma (Cheson, et al). CR is defined as a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. A post-treatment residual mass of any size is permitted as long as it is PET negative. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. A PR is defined as At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen.
Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks
Secondary Outcomes (7)
Number of Participants With Adverse Events Possibly Related to Study Drug Graded 3, 4, and 5
From time of treatment to 30 days post discontinuation (range of cycles attempted from induction +/- consolidation, & maintenance = 1-17 cycles) About 1 year Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks
Percentage of Participants Without Progression (Progression Free Survival (PFS))
start of treatment to time of progression (up to 2 years after treatment discontinuation)
Percentage of Participants Alive at 2 Years (Overall Survival)
From start of treatment to 2 years post treatment discontinuation
Number of Participants With Best Overall Response (BOR)
Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks
Number of Participants With Epstein Barr Virus (EBV) Activation and Number of Participants Without EBV Activation
Time from start of study treatment to last dose of study drug (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles, up to 1 year) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks
- +2 more secondary outcomes
Study Arms (1)
Treatment (brentuximab vedotin, rituximab)
EXPERIMENTALINDUCTION: Patients receive brentuximab vedotin IV over 30 minutes once weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve CR may receive additional optional consolidation therapy identical to induction therapy. MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histologically confirmed CD30+ and/or EBV+ lymphoid malignancy; in addition, there must be evidence of CD20 expression (at any level)
- In cases of post-transplant lymphoproliferative disorder (PTLD) arising in patients who are pharmacologically immunosuppressed, reduction of immunosuppression (RI) must be attempted prior to or in conjunction with enrollment, with the exception of those for whom RI would pose excessive threat of clinically significant graft rejection (as judged by local investigator)
- No prior chemotherapy or radiotherapy for PTLD or diffuse large B-cell lymphoma (DLBCL), with the exception of corticosteroids for 10 or fewer days at any dose (no washout period required)
- No prior surgical intervention, unless performed for the sake of tissue diagnosis or on an urgent basis for disease-related threat to life, limb, or organ function
- Bi-dimensionally measurable disease (at least 1 cm)
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Absolute neutrophil count \>= 750/mcL
- Platelets \>= 50,000/mcl
- Total bilirubin =\< 2 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase \[SPGT\]) =\< 3 X institutional ULN
- Creatinine =\< 2 X institutional ULN
- NOTE: Patients who do not meet the above criteria because of disease involvement of the organ in question, or because of acute systemic illness due to lymphoma, may enroll with permission of the study Principal Investigator (PI) and approval from the Data Monitoring Committee; this flexibility be allowed due to the heterogeneity of the patient population, the wide range of complications seen in the initial presentation of EBV-related malignancy, and the frequent difficulty encountered in attempting to clearly document that organ dysfunction is the result of an underlying lymphoproliferative disorder
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- +3 more criteria
You may not qualify if:
- Chemotherapy (including monoclonal antibodies) or radiotherapy, administered for any condition, within 4 weeks prior to entering the study or incomplete recovery from adverse events due to agents administered more than 4 weeks earlier
- Ongoing treatment with any other investigational agents
- Known central nervous system (CNS) involvement of lymphoma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to brentuximab vedotin and/or rituximab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Known human immunodeficiency virus (HIV) infection
- Known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
- Clinically active hepatitis A, B, or C infections; NOTE: patients with chronic hepatitis C (HCV) or hepatitis B (HBV) infection may enroll if other laboratory criteria are met; those with HBV surface antigen positivity may enroll only if maintained on appropriate suppressive antiviral therapy, per treating investigator's discretion, for the duration of enrollment in the trial
- Pregnancy or active nursing of an infant
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- Seagen Inc.collaborator
Study Sites (3)
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago
Chicago, Illinois, 60637, United States
Tufts University School of Medicine
Boston, Massachusetts, 02111, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study did not meet it's accrual goal of 33 patients. The study closed due to lack of funding.
Results Point of Contact
- Title
- Barbara Pro, MD
- Organization
- Northwestern University, Feinberg School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Adam Petrich, MD
Northwestern University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- MD
Study Record Dates
First Submitted
February 27, 2013
First Posted
March 5, 2013
Study Start
March 5, 2013
Primary Completion
September 18, 2017
Study Completion
December 31, 2018
Last Updated
September 1, 2021
Results First Posted
January 5, 2021
Record last verified: 2021-08