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.

Phase 1

Conditions: Hodgkin’s Lymphoma
MedDRA version: 17.0Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2013-003934-33-IT

Lead Sponsor: Fondazione Italiana Linfomi Onlus

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 13

Inclusion Criteria

1. Classical Hodgkin Lymphoma according to the World Health
Organisation (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 performance status of 0-2
8. Life expectancy > 6 months.
9. Written informed consent was obtained from the patient prior to any
study-specific screening procedures
10. Patients must be available for periodic blood sampling, study-related
assessments and management of toxicity at the treating institution
11. Females of childbearing potential must have a negative ß-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

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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

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 who have been 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
(see Appendix E)
• 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 (PML).
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 clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the activity of brentuximab vedotin in terms of complete remission (CT scan and FDG-PET negative) in patients with relapsed/refractory Hodgkin’s Lymphoma not responding (FDG-PET positive) to salvage treatment with IGEV. ;Secondary Objective: To evaluate if brentuximab vedotin administration after unsatisfactory response to IGEV is able to achieve CR, thus improving progression free survival (PFS) and duration of remission. <br> <br>To evaluate the toxicity of brentuximab vedotin in terms of haematological and extra-haematological side effects according to the NCI CTCAE (Version 4.03).<br> <br> ;Primary end point(s): CR rate;Timepoint(s) of evaluation of this end point: 1 year and half from the beginning of the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Toxicity and PFS;Timepoint(s) of evaluation of this end point: Toxicity: 1 year and half from the beginning of the study<br>PFS: 2 years and half from the beginning of the study