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

Primary Purpose

Peripheral T-cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Romidepsin + Gemcitabine
Sponsored by
Fondazione Italiana Linfomi - ETS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral T-cell Lymphoma focused on measuring T-cell lymphoma, Romidepsin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • A.O. SS. Antonio e Biagio e C. Arrigo
  • Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Romidepsin, Gemcitabine

Arm 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 (progression disease)

Outcomes

Primary Outcome Measures

Complete Remission (CR) Rate
Complete Remission is disappearance of all target lesions per the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007)"

Secondary Outcome Measures

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.
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.
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).
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).

Full Information

First Posted
March 28, 2013
Last Updated
October 11, 2019
Sponsor
Fondazione Italiana Linfomi - ETS
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1. Study Identification

Unique Protocol Identification Number
NCT01822886
Brief Title
Phase II Study of Gemcitabine+Romidepsin in the Relapsed/Refractory Peripheral T-cell Lymphoma Patients
Acronym
FIL_GEMRO
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
January 2013 (Actual)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Italiana Linfomi - ETS

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral T-cell Lymphoma
Keywords
T-cell lymphoma, Romidepsin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Romidepsin, Gemcitabine
Arm Type
Experimental
Arm 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 (progression disease)
Intervention Type
Drug
Intervention Name(s)
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
Primary Outcome Measure Information:
Title
Complete Remission (CR) Rate
Description
Complete Remission is disappearance of all target lesions per the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007)"
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Percentage of Participants With Progression-Free Survival
Description
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.
Time Frame
24 months
Title
Overall Survival is Measured From the Date of Study Entry to the Date of Patient's Death
Description
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.
Time Frame
24 months
Title
Safety - Frequency of Toxicities Grade 3 and 4
Description
Frequency of toxicities was reported by type and grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).
Time Frame
24 months
Title
Overall Response Rate (ORR)
Description
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).
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pier Luigi Zinzani
Organizational Affiliation
Istituto Ematologia e Oncologia Medica "SERAGNOLI" Università di Bologna
Official's Role
Principal Investigator
Facility Information:
Facility Name
A.O. SS. Antonio e Biagio e C. Arrigo
City
Alessandria
ZIP/Postal Code
15121
Country
Italy
Facility Name
Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
27071522
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.
Results Reference
derived

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

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