Phase II Study of Gemcitabine+Romidepsin in the Relapsed/Refractory Peripheral T-cell Lymphoma Patients
Condition: Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Romidepsin + Gemcitabine
Intervention description: Romidepsin 12 mg/m2 day 1,8, 15 + Gemcitabine 800 mg/m2 day 1, 15 for 6 cycles by 28 days followed by Romidepsin 14 mg/m2 day 1, 15 to PD
Intervention MeSH terms: Gemcitabine; Romidepsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: T-cell lymphoma; Romidepsin

Summary:

      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.
    

Eligibility criteria:

        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