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

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

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

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Romidepsin + Gemcitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romidepsin, Gemcitabine<br>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<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-cell lymphoma, Romidepsin