Study on the Role of Brentuximab Vedotin as Single Agent in the Treatment of Relapsed/Refractory CD30+ PTCL Patients

Phase II Study on the Role of Brentuximab Vedotin as Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T Cell Lymphoma (PTCL) Patients

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.