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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Romidepsin + Gemcitabine

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • A.O. SS. Antonio e Biagio e C. Arrigo
  • Bologna, Italy, 40138
    • Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Torino, Italy, 10126
    • A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romidepsin, Gemcitabine; 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 (progression disease)	Drug: Romidepsin + Gemcitabine; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission (CR) Rate	Complete Remission is disappearance of all target lesions per the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007)"	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression-Free Survival	The time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS (progression-free survival) data will be censored on the day following the date of the last radiological assessment of measured lesions documenting absence of progressive disease for patients who do not have objective tumor progression and are still on study at the time of an analysis, are given antitumor treatment other than the study treatment or stem cell transplant, or are removed from study prior to documentation of objective tumor progression. Patients lacking an evaluation of tumor response after their first dose will have their event time censored at 1 day. Percentage of participants is an estimate based on Kaplan-Meier method.	24 months
Overall Survival is Measured From the Date of Study Entry to the Date of Patient's Death	OS (overall survival) is measured from the date of study entry to the date of patient's death. If the patient is alive or his vital status is unknown, the date of death will be censored at the date that the patient is last known to be alive.	24 months
Safety - Frequency of Toxicities Grade 3 and 4	Frequency of toxicities was reported by type and grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).	24 months
Overall Response Rate (ORR)	ORR the proportion of patients who achieve CR (complete response), CRu (complete remission unconfirmed) or PR (partial response) relative to the per-protocol population. Disease response and progression will be evaluated according to the "Revised Response Criteria" for malignant lymphoma (Cheson et al. 2007).	24 months

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi ONLUS
• Investigators: Principal Investigator: Pier Luigi Zinzani, Istituto Ematologia e Oncologia Medica "SERAGNOLI" Università di Bologna

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: March 28, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: T-cell lymphoma; Romidepsin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antibiotics, Antineoplastic; Gemcitabine; Romidepsin
• Other Study ID Numbers: FIL_GEMRO