This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and
safety of Brentuximab Vedotin (BV) as a single agent in relapsed/refractory CD30+ PTCL
patients.
BV will be administered as a single IV infusion on Day 1 of each 21-day cycle. Measures of
anti-cancer activity will be assessed using the revised response criteria for malignant
lymphoma (Cheson et al. 2007).
Computed tomography (CT) scans (chest, neck, abdomen, and pelvis) and PET scan will be
performed at baseline and Cycles 3, 8, 12, and 16. Patients will have an End of Treatment
(EOT) assessment 30 ± 7 days after receiving their final dose of study drug. Patients with at
least stable disease will enter short follow up phase till month 24 with radiology assessment
every 6 months and visit every 12 weeks. After month 24 and for all patients with progressive
disease, long-term follow-up assessments (including survival, disease status and next therapy
information) will be performed every 12 weeks until either patient death or study closure,
whichever occurs first.
Inclusion Criteria:
- Signed written informed consent.
- Males and females ≥18 and ≤75 years at the time of enrolment.
- Histologically confirmed diagnosis of PTCL (PTCL-not otherwise specified [PTCL-NOS],
angioimmunoblastic T cell lymphoma [AILT] and transformed mycosis fungoides) according
to World Health Organization (2008) classification.
- Histologically confirmed CD30+ PTCL.
- Availability of histological material for central review and pathobiological studies.
- Failed at least one prior systemic antilymphoma therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study
entry.
- At least one site of disease measurable in two dimensions by computed tomography. Both
nodal and extranodal disease will be considered (lymphnodes 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).
- Hematology values within the following limits:
- Absolute neutrophil count (ANC) ≥ 1500/mm3 independent of growth factor support.
- Platelets ≥75,000/mm3 or ≥50,000/mm3 if bone marrow involvement is independent of
transfusion support.
- Hemoglobin level ≥8 g/dL.
- Biochemical values within the following limits:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper
limit of normal (ULN).
- Total bilirubin < 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome
or of nonhepatic origin).
- Serum creatinine ≤ 2 x ULN.
- Serum albumin ≥ 3 g/dL.
- Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7
days of receiving study medication.
- WOCBP must agree to use effective contraception, defined as oral contraceptives,
double barrier method or practice true abstinence from sexual intercourse during the
study and for 6 months after the last dose of study drug.
- Male subjects and their female partners of childbearing potential must be willing to
use an appropriate method of contraception or practice true abstinence from sexual
intercourse during the study and for 6 months after the last dose of study drug.
Exclusion Criteria:
- Diagnosis of CTCL, ALCL, mycosis fungoides or Sezary Syndrome.
- CD30 expression < 10 %.
- 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.
- Patients underwent major surgery without complete recovery
- Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
contained in the drug formulation of brentuximab vedotin.
- Any serious active disease or co-morbid medical condition (according to investigator's
decision).
- 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.
- Patients with peripheral neuropathy of grade 3-4 (also grade 2 with persistent pain,
unresponsive to treatment).
- Signs or symptoms of progressive multifocal leukoencephalopathy (PML).
- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
- 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.
- CNS disease (meningeal and/or brain involvement by lymphoma) or testicular
involvement.
- History of clinically relevant liver or renal insufficiency; significant cardiac,
vascular pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic,
hematologic, psychiatric, or metabolic disturbances.
- Known history of any of the following cardiovascular conditions:
- Myocardial infarction within 2 years from enrollment
- 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%
- Active opportunistic infection.
- Known history of Human Immunodeficiency Virus (HIV) or Hepatitis C or active infection
with Hepatitis B.
- Prior allogeneic stem cell transplant.
