A phase II study with bendamustine plus brentuximab vedotin in Hodgkin’s lymphoma and CD30+ peripheral T-cell lymphoma in first salvage setting: the BBV regimen.
- Conditions
- Hodgkin’s lymphoma and CD30+ peripheral T-cell lymphomaMedDRA version: 22.0Level: LLTClassification code 10012877Term: Diffuse large cell lymphoma (Peripheral T-cell lymphoma unspecified) (Working Formulation) recurrentSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005382-79-IT
- Lead Sponsor
- FONDAZIONE ITALIANA LINFOMI ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 65
4.1. Inclusion criteria for patients with classical Hodgkin’s lymphoma
1) Patients at first relapse or with primary refractory disease (i.e. patients who have previously
received only 1 line of treatment). Patients must have completed any prior treatment with
radiation, chemotherapy, biologics, immunotherapy and/or other investigational agents at
least 4 weeks prior to the first BBV dose
2) Histologically-confirmed CD30+ disease (IHC BerH2 antibody)
3) Age from 18 to 60 years.
4) Fluorodeoxyglucose (FDG)-avid and measurable disease (lymph nodes must have long axis
of 1.5 cm regardless of short axis or long axis 1.1 to 1.5 and short axis > 1.0 cm) as
documented by both PET and CT.
5) An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6) The following required baseline laboratory data: absolute neutrophil count (ANC) =
1500/µL, unless known marrow involvement due to disease, platelets = 75,000/µL, unless
known marrow involvement due to disease, bilirubin = 1.5 x upper limit of normal (ULN) or
= 3 x ULN for patients with Gilbert’s disease, serum creatinine = 1.5 X ULN, alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 X ULN.
7) Serum Albumin = 3 g/dL.
8) Females of childbearing potential must have a negative serum or urine ß-hCG pregnancy
test result within 7 days prior to the first dose of therapy. Females of non-childbearing
potential are those who are postmenopausal for more than 1 year or who have had a bilateral
tubal ligation or hysterectomy.
9) Both 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 at
least 6 months following the last dose of study drug.
10) Male patients, even if surgically sterilized (i.e., post vasectomy), who:
•Agree to practice effective barrier contraception during the entire study treatment
period and through 6 months after the last dose of the study drug, or
•Agree to completely abstain from heterosexual intercourse
11) Patients must provide written informed consent.
4.3. Inclusion criteria for patients with peripheral T-cell lymphomas
1) Patients with refractory or relapsed PTCL regardless of the number of prior therapy lines.
Patients must have completed any prior treatment with radiation, chemotherapy, biologics,
immunotherapy and/or other investigational agents at least 4 weeks prior to the first dose of
therapy.
2) Signed written informed consent.
3) Age from 18 to 60 years.
4) Histologically confirmed diagnosis of PTCL, i.e. PTCL-not otherwise specified (PTCLNOS),
angioimmunoblastic T cell lymphoma (AITL) and transformed mycosis fungoides
according to the World Health Organization (WHO) 2008 classification.
5) Histologically confirmed CD30+ PTCL (IHC BerH2 antibody).
6) Eastern Cooperative Oncology Group (ECOG) performance status score of = 1 at study
entry.
7) At least one site of measurable disease in two dimensions by computed tomography. Both
nodal and extranodal sites will be taken into consideration (lymph nodes must have long
axis of 1.5 cm regardless of short axis or long axis 1.1 to 1.5 cm and short axis > 1.0 cm).
8) Hematology values within the following limits:
a. absolute neutrophil count (ANC) = 1500/mm3 independent of growth factor support;
b. platelets = 75,000/mm3 or = 50,000/mm3 if bone marrow involvement is independent
of transfusion support;
c. hemoglobin level = 8 g/dL.
9) Biochemical values within the following limits:
4.2. Exclusion criteria for patients with classical Hodgkin’s lymphoma
1) Previous treatment with bendamustine or brentuximab vedotin.
2) Prior autologous stem cell transplant.
3) Known history of any of the following cardiovascular conditions: myocardial infarction
within 2 years of study entry; NYHA class III or IV heart failure; cardiac arrhythmias;
angina; any electrocardiographic evidence of acute ischemia or conduction system
abnormalities; recent evidence (within 6 months before the first dose of study drug) of a leftventricular ejection fraction < 50%.
4) History of another primary malignancy for within 3 years of study entry (the following are
exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized
prostate cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion
on PAP smear).
5) Known cerebral/meningeal disease (HL or any other etiology) or testicular involvement.
6) Signs or symptoms of progressive multifocal leukoencephalopathy (PML).
7) Pre-existing Peripheral Neuropathy = 2.
8) Any active systemic viral, bacterial, or fungal infection requiring treatment with
antimicrobial therapy within 2 weeks prior to the first dose of therapy.
9) Current therapy with other systemic anti-neoplastic or investigational agents.
10) Therapy with corticosteroids at greater than or equal to 20 mg/day prednisone equivalent
within 1 week prior to the first dose of therapy.
11)Women who are pregnant or breastfeeding.
12) Patients with a known hypersensitivity to recombinant proteins, murine proteins, or any
excipient contained in the drug formulation of brentuximab vedotin and to bendamustine.
13)Known human immunodeficiency virus (HIV) positivity.
14)Known hepatitis B surface antigen (HBsAg) positivity or known or suspected active
hepatitis C infection.
15) Patients with dementia or altered mental state that would preclude the understanding and
rendering of informed consent.
4.4. Exclusion criteria for patients with peripheral T-cell lymphomas
1) Diagnosis of cutaneous T-cell lymphoma, anaplastic large-cell lymphoma (ALCL), mycosis
fungoides or Sézary Syndrome.
2) Previous treatment with bendamustine or brentuximab vedotin.
3) Prior autologous stem cell transplant.
4) Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
contained in the drug formulation of brentuximab vedotin and to bendamustine.
5) Any serious active disease or co-morbid medical condition (according to investigator's
decision).
6) Prior history of malignancies other than lymphoma (except for a history of a complete
resection for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the
cervix or breast) unless the subject has been free of the disease for = 3 years.
7) Pre-existing peripheral neuropathy grade = 2.
8) Signs or symptoms of progressive multifocal leukoencephalopathy (PML).
9) Any serious medical condition, laboratory abnormality, or psychiatric illness that would
prevent the subject from signing the informed consent form.
10) Pregnant or lactating females or men or women of childbearing potential not willing to use
an adequate method of birth control for the duration of the study or a positive pregnancy test
on day 1 before first dose of study drug.
11) Central nervous system disease (meningeal and/or brain involvement by lymphoma) or
testicular involvement.
12)History of clinically relevant liver or renal insufficiency; significant pulmonary,
gastrointe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the antitumor efficacy, in terms of overall response rate, of bendamustine in combination with brentuximab vedotin in Hodgkin’s lymphoma and CD30+ PTCL as a first salvage treatment.;Secondary Objective: To assess the safety and tolerability of the BBV regimen, to evaluate clinical improvement and patients’ survival.;Primary end point(s): overall objective response rate (ORR). <br>;Timepoint(s) of evaluation of this end point: 6 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): the complete remission (CR) rate; the progression-free survival (PFS) and overall survival (OS) ; the type, incidence, severity, seriousness, of adverse events and laboratory abnormalities observed during treatment and the assessment of any potential relationship to the study drugs.; the duration of the response (DOR); ;Timepoint(s) of evaluation of this end point: 6 months; 1 year; 54 months; 4