Phase II Study of Gemcitabine+Romidepsin in the Relapsed/Refractory Peripheral T-cell Lymphoma Patients

Phase IIa Study on the Role of Gemcitabine Plus Romidepsin (GEMRO Regimen) in the Treatment of Relapsed/Refractory Peripheral T-cell Lymphoma Patients.

Pilot clinical trial - Phase 2a, multicenter, single arm, open label trial - to evaluate efficacy and safety of concomitant combination treatment with Gemcitabine and Romidepsin (GEMRO) regimen as salvage treatment in relapsed/refractory PTCL (peripheral T-cell lymphoma) in a selected population of patients.

Objectives will be focused on preliminary dose-response, type of patients, frequency of dosing, and safety and tolerability profile.

Inclusion Criteria:

• Patients with histological diagnosis of PTCL according to the WHO (World Health Organization) classification

• Age ≥ 18 years

• Relapsed (≥1) or refractory to conventional chemotherapy/radiotherapy

• Stage I-IV according to the Ann Arbor staging System

• ECOG (Eastern Cooperative Oncology Group) Performance status ≤2

• Normal renal and hepatic functions

• Laboratory test results as follows:

  • Serum creatinine ≥ 2.0 mg/dL
  • Total bilirubin ≥ 1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) £2 x ULN or £5 x ULN if hepatic metastases are present
  • Negative HIV HCV and HBV status

• Adequate bone marrow reserve: Platelet count>100X109 cells/L or platelet count <75X109 cells/L if bone marrow disease involvement, absolute neutrophile count (ANC)> 1,5 X109, hemoglobin>8 g/dl.

• Able to adhere to the study visit schedule and other protocol requirements

• Cardiac ejection fraction (MUGA scan or echocardiography) > 45%

• Life expectancy > 6 months

• Females of childbearing potential (FCBP) must have a negative serum or urine β-hCG pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy

• 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 30 days after the last dose of study drug.

• Measurable disease of at least 2 cm as detected by CT scan, assessed by site radiologist

• Patients or they legally authorized representative must provide written informed consent

Exclusion Criteria:

• Any serious active disease or co-morbid medical condition (according to investigator's decision)
• Prior history of malignancies other than lymphoma (except 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
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Patients with congenital long QT syndrome, history of significant cardiovascular disease and/or taking drugs leading to significant QT prolongation
• Corrected QT interval > 480 msec (using the Fridericia formula)
• Low K+ (<3.8 mmol/L) and low Mg+ (<0.85 mmol/L) levels, except if corrected before beginning the chemotherapy
• 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
• Previous exposure to romidepsin or gemcitabine
• 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
• Active opportunistic infection