Pilot Study of Brentuximab Vedotin in Relapsed/Refractory Peripheral T-Cell Lymphoma Expressing CD30

Peripheral T-Cell Lymphoma Clinical Trial

Official title:

Pilot Study of Brentuximab Vedotin in Relapsed/Refractory Peripheral T-Cell Lymphoma Expressing CD30 Receptor

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01841021
• Other study ID #: MCC-17343
• Secondary ID: 35-IST-019
• Status: Terminated
• Phase: N/A
• First received: April 24, 2013
• Last updated: November 15, 2016
• Start date: April 2014
• Est. completion date: June 2016

Study information

• Verified date: November 2016
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to test if brentuximab vedotin has an effect on cancer in patients with a certain type of large B-cell lymphoma. The side effects (unwanted effects) of SGN-35 in patients with this certain type of large B-cell lymphoma will also be studied. It is not known if brentuximab vedotin is better or worse than other treatment patients might be given.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of PTCL expressing CD30 receptor. Following PTCL subtypes will be eligible: Peripheral T - cell lymphoma, not otherwise specified (NOS); Angioimmunoblastic T-cell Lymphoma; Subcutaneous Panniculitis Like T-cell Lymphoma; Hepatosplenic gamma/delta T cell Lymphoma; Extranodal natural killer (NK)T-cell Lymphoma, nasal type; Enteropathy-associated T-cell lymphoma; Adult T-cell Leukemia/lymphoma; T-cell prolymphocytic leukemia; Primary cutaneous gamma-delta T-cell lymphoma; Aggressive NK cell leukemia; Aggressive subtype of T cell Large Granular Lymphocytic (LGL) or transformed LGL leukemia; Epstein Barr Virus(EBV)-positive T-cell lymphoproliferative disorders of childhood; Transformed mycosis fungoides who have progressed following treatment with at least one systemic therapy; Sezary syndrome

• Histology slides and pathology material must be available at the site for each patient before enrollment in order to be sent to the Leading Institution of the study for central pathology review and pharmacodynamic studies.

• Patients must have progressive, relapsed or refractory disease after: At least one prior systemic anti-lymphoma regimen (chemotherapy or immunotherapy except for transformed mycosis fungoides as described previously); Relapsed or failed autologous or allogeneic stem cell transplant.

• Understand and voluntarily sign an Institutional Review Board (IRB) approved informed consent form

• Must have at least one site of disease (index lesion) measurable in two dimensions by computed tomography (CT)

• Patients with leukemic form of PTCL who will not have a measurable lesion in two dimensions by CT scan, relapsed or refractory disease must be detected by immunohistochemistry or flow cytometry and molecular clonality studies in bone marrow or peripheral blood.

• At least 2 weeks since the last chemotherapy, radiation therapy, immunotherapy or any investigational products

• Must meet the following criteria within 4 days before the first dose of study drug:

• Neutrophils =1,000/ul

• Hemoglobin = 8 g/dL

• Platelets= 50.0x10^9 /L

• Total bilirubin = 1.5 x upper normal limit, or = 5 x upper normal limit if documented hepatic involvement with lymphoma or history of Gilbert's Syndrome

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x upper normal limit (= 5 x upper normal limit if documented hepatic involvement with lymphoma)

• Calculated creatinine clearance = 40 mL/min/1.73 m^2 based on Cockcroft and Gault method

• PT or International Normalization Ratio (INR), and Activated Partial Thromboplastin Time (APTT) = 1.5 x upper limit of normal unless patient is receiving anticoagulants. If patient is on anticoagulation therapy, levels should be within therapeutic range.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Negative pregnancy test for women of childbearing potential

• Recovered (= Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy

Exclusion Criteria:

• Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: Myocardial infarction and the New York Heart Association (NYHA) Class III or IV heart failure

• History of another primary malignancy not in clinical remission; except adequately treated patients with completely resected in situ carcinoma, such as nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, or localized prostate cancer with prostate-specific antigen (PSA) <1 ng/ml

• Known active cerebral/meningeal involvement with lymphoma. Asymptomatic patients with previously treated and resolved central nervous system (CNS) lymphoma involvement are permitted.

• Prior administration of Brentuximab vedotin

• Corticosteroid monotherapy for lymphoma within 1 week of the first dose of study drug

• Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair the ability to receive or tolerate the planned treatment

• Known hypersensitivity to recombinant proteins, or any component contained in the drug formulation

• Female patients who are lactating or have a positive serum pregnancy test during the screening period

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-Cell Lymphoma

Intervention

Drug:
• Brentuximab vedotin
Brentuximab vedotin will be given by intravenous infusion (into a vein) on Day 1 of every 21 day cycle.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	To evaluate the activity of Brentuximab vedotin in patients with relapsed/refractory Peripheral T cell Lymphoma (PTCL) expressing CD30 receptor. The ORR [complete response (CR)+ partial response (PR)] will be used as the primary endpoint to assess efficacy.The primary efficacy parameter is objective response rate, defined as the proportion of patients with complete response (CR) and partial response (PR). Follow-up assessments after cycle 16 will be done every 12 weeks for up to 24 months. Restaging imaging computed tomography (CT) scans will be repeated 12 and 24 months from the beginning of the follow-up period. Objective disease response (CR and PR) will be defined according to the modified 2007 International Working Group (IWG) response criteria for non-Hodgkin lymphomas (NHL). CR = Disappearance of all evidence of disease; PR = Regression of measurable disease and no new sites.	4 years	No
Secondary	Median Time to Response	Objective disease response (CR and PR), stable disease (SD) and progressive disease (PD) will be defined according to the modified 2007 International Working Group (IWG) response criteria for non-Hodgkin lymphomas (NHL).	4 years	No
Secondary	Duration of Response	Objective disease response (CR and PR), stable disease (SD) will be defined according to the modified 2007 International Working Group (IWG) response criteria for non-Hodgkin lymphomas (NHL).	4 years	No
Secondary	Median Time to Disease Progression	Progressive disease (PD) will be defined according to the modified 2007 International Working Group (IWG) response criteria for non-Hodgkin lymphomas (NHL).	4 years	No
Secondary	Number of Participants with Progression Free Survival (PFS)	Stable disease (SD) will be defined according to the modified 2007 International Working Group (IWG) response criteria for non-Hodgkin lymphomas (NHL).	4 years	No
Secondary	Number of Participants with Overall Survival (OS)	Radiological assessments will be discontinued at the time of tumor progression or initiation of new anticancer therapy, after which survival will be evaluated every 3 months until 2 years from the start of study treatment or until study closure.	4 years	No
Secondary	Number of Participants with Study Related Serious Adverse Events (SAEs)	Adverse events (AEs) will be summarized by worst NCI NCI Common Terminology Criteria for Adverse Events (CTCAE) grade. The patient incidence of AEs will be summarized by system organ class, preferred term, severity and relationship to study drug. Adverse events leading to death or to discontinuation from treatment, events classified as CTCAE 4.0 grade 3 or higher, study-drug-related events, and serious adverse events (SAEs) will be listed separately.	4 years	Yes

External Links

•   Moffitt Cancer Center Clinical Trials website