BRENTUXIMAB VEDOTIN as Pre-ASCT Induction Therapy in R/R HL Patients Non Responding to IGEV

Phase 2

Completed

• Conditions: Relapsed/Refractory Hodgkin's Lymphoma
• Interventions: Drug: BRENTUXIMAB VEDOTIN

• Registration Number: NCT02244021
• Lead Sponsor: Fondazione Italiana Linfomi - ETS

Brief Summary

A pilot phase II study with brentuximab vedotin as pre-ASCT induction therapy in relapsed/refractory Hodgkin's lymphoma patients non-responding to IGEV salvage treatment.

Detailed Description

Brentuximab vedotin emerged as active single-agent in the treatment of relapsed or refractory HL.

Some patients don't reach a complete response after salvage treatment with IGEV (ifosfamide, gemcitabine, vinorelbine) and remain PET positive so the idea is to treat this subset of patients with brentuximab vedotin with the aim of achieving a complete remission before transplant.

Study Timeline

• Study First Submitted: 2014-09-10
• Study First Submitted QC: 2014-09-16
• Study First Posted: 2014-09-18
• Study Start: 2014-12
• Primary Completion: 2016-07
• Study Completion: 2017-10
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-08
• Last Update Posted: 2018-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Classical Hodgkin Lymphoma according to the WHO classification
2. Histologically confirmed CD30+ HL at diagnosis
3. Patients at the first line salvage therapy
4. FDG-PET positivity after two cycles of IGEV treatment
5. PBPCs should have been collected after the first or the second IGEV cycle
6. Age≥ 18 years
7. ECOG PS of 0-2
8. Life expectancy > 6 months.
9. Written informed consent
10. Patients available for periodic blood sampling, study-related assessments and management of toxicity
11. Females of childbearing potential must have a negative β-HCG pregnancy test result (pregnancy test should be performed at screening an on day 1 of cycle 1 prior to brentuximab vedotin treatment).
12. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
13. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
14. Required baseline laboratory data: Absolute neutrophil count ≥ 1500/µl, Platelet count ≥ 75.000/ µl, Haemoglobin must be ≥ 8 g/dL, Serum bilirubin ≤ 1.5 times ULN, Serum creatinine < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN

Exclusion Criteria

1. Peripheral neuropathy > Grade 1
2. Histologic diagnosis different from Hodgkin Lymphoma
3. First line treatment with BEACOPP
4. Compressive symptoms caused by the presence of Lymphoma
5. Patients treated previously with any anti-CD30 antibody.
6. Known hypersensitivity to any recombinant proteins, murine proteins, or excipients contained in the brentuximab vedotin formulation.
7. Known human immunodeficiency virus (HIV) positive
8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
9. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
10. Patients with known history of any of the following cardiovascular conditions:Myocardial infarction within 2 years of randomization, New York Heart Association (NYHA) Class III or IV heart failure, Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%
11. Patients with known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 2 weeks prior to the first dose of brentuximab vedotin.
12. Patients with known active Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin.
13. Patients with known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy
14. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol.
15. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
16. Patients who are pregnant, or lactating and breastfeeding.
17. Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BRENTUXIMAB VEDOTIN	BRENTUXIMAB VEDOTIN	1 arm for all patients

Primary Outcome Measures

Name	Time	Method
Complete response (CR rate)	1 year and half from the beginning of the study	Complete response will be defined according to recently updated international criteria (Cheson 2007), assuming that a negative PET is defined by DEAUVILLE scores 1 and 2.

Secondary Outcome Measures

Name	Time	Method
PFS	2 years and half from the beginning of the study	Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of progression free survival (PFS).
Duration of remission (DR)	2 years and half from the beginning of the study	Additional study endpoint is final response to Brentuximab vedotin followed by autologous stem cell transplantation (ASCT), in terms of duration of remission (DR).
Neurotoxicity rate	1 year half from the beginning of the study	Neurotoxicity of any grade defined as National Cancer Institute Common Terminology Criteria for Adverse Events , version 4.03 (NCI CTCEA, 2010)

Trial Locations

Locations (7)

Ematologia, IRCCS AOU San Martino-IST; 🇮🇹 Genova, Italy

SC Ematologia - Azienda Ospedaliera AO Città della Salute e della Scienza; 🇮🇹 Torino, Italy

Istituto di Ematologia "L. & A. Seragnoli" , Policlinico S. Orsola Malpighi; 🇮🇹 Bologna, Italy

Ematologia Ospedale Vito Fazzi; 🇮🇹 Lecce, Italy

Università degli Studi di Modena e Reggio Emilia, D.A.I di Medicina diagnostica clinica e sanità pubblica, AOU Policlinico; 🇮🇹 Modena, Italy

Ematologia e Unità BMT IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas; 🇮🇹 Rozzano, Italy