Clinical trial NCT02244021: BRENTUXIMAB VEDOTIN as Pre-ASCT Induction Therapy in R/R HL Patients Non Responding to IGEV
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed/Refractory Hodgkin's Lymphoma
Keywords: HD
Hodgkin's Lymphoma
RELAPSED-REFRACTORY
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2014-09-18
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete response (CR rate)
timeFrame: 1 year and half from the beginning of the study
Secondary outcomes:
measure: PFS
timeFrame: 2 years and half from the beginning of the study
measure: Neurotoxicity rate
timeFrame: 1 year half from the beginning of the study
measure: Duration of remission (DR)
timeFrame: 2 years and half from the beginning of the study
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Istituto di Ematologia "L. & A. Seragnoli" , Policlinico S. Orsola Malpighi
city: Genova
country: Italy
facility: Ematologia, IRCCS AOU San Martino-IST
city: Lecce
country: Italy
facility: Ematologia Ospedale Vito Fazzi
city: Milano
country: Italy
facility: Ematologia e Unità BMT IRCCS Istituto Nazionale dei Tumori
city: Modena
country: Italy
facility: Università degli Studi di Modena e Reggio Emilia, D.A.I di Medicina diagnostica clinica e sanità pubblica, AOU Policlinico
city: Rozzano
country: Italy
facility: Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas
city: Torino
country: Italy
facility: SC Ematologia - Azienda Ospedaliera AO Città della Salute e della Scienza
Study officials:
affiliation: Hematology Division, IRCCS AOU San Martino, Genova, Italy
name: Angelo Michele Carella, Prof.
role: PRINCIPAL_INVESTIGATOR
References: