Clinical trial NCT01822886: Phase II Study of Gemcitabine+Romidepsin in the Relapsed/Refractory Peripheral T-cell Lymphoma Patients
Official title: Phase IIa Study on the Role of Gemcitabine Plus Romidepsin (GEMRO Regimen) in the Treatment of Relapsed/Refractory Peripheral T-cell Lymphoma Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral T-cell Lymphoma
Keywords: T-cell lymphoma
Romidepsin
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2013-04-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

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

Primary outcomes:
measure: Complete Remission (CR) Rate
timeFrame: 18 months
Secondary outcomes:
measure: Percentage of Participants With Progression-Free Survival
timeFrame: 24 months
measure: Overall Survival is Measured From the Date of Study Entry to the Date of Patient's Death
timeFrame: 24 months
measure: Safety - Frequency of Toxicities Grade 3 and 4
timeFrame: 24 months
measure: Overall Response Rate (ORR)
timeFrame: 24 months
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e C. Arrigo
city: Bologna
country: Italy
facility: Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Torino
country: Italy
facility: A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino
Study officials:
affiliation: Istituto Ematologia e Oncologia Medica "SERAGNOLI" Università di Bologna
name: Pier Luigi Zinzani
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pellegrini C, Dodero A, Chiappella A, Monaco F, Degl'Innocenti D, Salvi F, Vitolo U, Argnani L, Corradini P, Zinzani PL; Italian Lymphoma Foundation (Fondazione Italiana Linfomi Onlus, FIL). A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients. J Hematol Oncol. 2016 Apr 12;9:38. doi: 10.1186/s13045-016-0266-1.