A study to compare the safety and efficiacy of Brentuximab Vedotin when given with Bendamustine and Rituximab, compared to Bendamustine and Rituximab only in patients with relapsed or refactory CD-30 positive diffuse large B cell lymphoma

Phase 1

Conditions: Relapsed or Refractory CD30-Positive Diffuse Large B-Cell Lymphoma
MedDRA version: 18.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0Level: LLTClassification code 10067070Term: Follicular B-cell non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-001671-51-FR

Lead Sponsor: Seattle Genetics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 110

Inclusion Criteria

1. Patients with histologically confirmed CD30-positive DLBCL or follicular non-Hodgkin lymphoma (NHL) grade 3b, defined as any detectable CD30 expression on tumor cells based on local pathologic assessment.
2. Patients must have relapsed or refractory disease following:
a. second-line or greater salvage systemic therapy, or
b. frontline cytotoxic systemic therapy, for patients who are ineligible for stem cell transplant (SCT).
3. Age 18 and older.
4. Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist.
5. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2.
6. The following baseline laboratory data:
a. Absolute neutrophil count (ANC) =1000/µL (unless documented bone marrow involvement)
b. Platelet count =50,000/µL (unless documented bone marrow involvement)
c. Serum bilirubin =1.5 × upper limit of normal (ULN) or =3 × ULN for patients with Gilbert’s disease
d. Estimated creatinine clearance (CrCL) =40 mL/min (calculated using the Cockcroft-Gault formula)
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 × ULN.
7. Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 7 days prior to the first dose of study drug.
Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or bilateral oophorectomy or hysterectomy.
8. Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of brentuximab vedotin or 12 months following the last dose of rituximab, whichever is later.
9. Patients or their legally authorized representative must provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

Exclusion Criteria

1. History of another invasive malignancy that has not been in remission for at least 1 year. The following are exempt from the 1-year limit: nonmelanoma skin cancer, curatively treated localized prostate cancer, ductal carcinoma in situ (DCIS), and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.
2. History of progressive multifocal leukoencephalopathy (PML).
3. Cerebral/meningeal disease related to the underlying malignancy. Patients with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior central nervous system (CNS) disease has been definitively treated.
4. Any active Grade 3 or higher (per the National Cancer Institute [NCI, US] Common Terminology Criteria for Adverse Events [CTCAE] Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin. Routine antimicrobial prophylaxis is
permitted.
5. Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of study drug.
6. Females who are pregnant or breastfeeding.
7. Known hypersensitivity to any study drug or excipient contained in the drug formulation of any of the study drugs.
8. Known to be positive for hepatitis B by surface antigen expression (HBsAg) and hepatitis B core antibody (HBcAb). Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within the last 6 months.
9. Known to be positive for human immunodeficiency virus (HIV).
10. Patients with previous allogeneic SCT.
11. Previous treatment with brentuximab vedotin or bendamustine.
12. Intolerable toxicity to prior rituximab therapy (per Investigator discretion).
13. Current therapy with other investigational agents.
14. Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
15. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association
(NYHA) Class III-IV within 6 months prior to the first dose of brentuximab vedotin.
16. Congestive heart failure, Class III or IV, by the NYHA criteria.
17. Grade 2 or higher (per NCI CTCAE, Version 4.03) peripheral sensory or motor neuropathy at baseline.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the objective response rate (ORR) between the 2 arms;Secondary Objective: -To compare progression-free survival (PFS) between the 2 arms<br>-To compare the complete remission (CR) rate between the 2 arms<br>-To compare duration of response (DOR) between the 2 arms<br>-To compare overall survival (OS) between the 2 arms<br>-To evaluate the safety and tolerability of the 2 arms<br>;Primary end point(s): The primary efficacy endpoint of this study is objective response rate (ORR);Timepoint(s) of evaluation of this end point: Imaging (CT and PET or CT/PET; PET no longer required after documented postbaseline FDG-negative PET) at the end of Cycles 2 and 6; 6, 12, and 24 months after the end of combination treatment; and<br>annually thereafter until disease progression or study closure).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoints are the following:<br>- Progression-free survival<br>- Complete remission rate<br>-Best clinical response<br>-Duration of response<br>-Overall survival<br>-Type, incidence, severity, seriousness, and relatedness of AEs<br>- Type, incidence, and severity of laboratory abnormalities<br>- Incidence and severity of infusion-related and hypersensitivity reactions.;Timepoint(s) of evaluation of this end point: Please refer to Table 2 of the study protocol (Study Schedule), page 42<br>of 91

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