E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory cutaneous T-cell lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011678 |
E.1.2 | Term | Cutaneous T-cell lymphoma recurrent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011679 |
E.1.2 | Term | Cutaneous T-cell lymphoma refractory |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary research question is to confirm the feasibility and efficacy of using a combination of Gemcitabine and Bexarotene for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have disease that is no longer controlled by skin-directed therapy and who have had at least one prior systemic therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objectives are firstly to evaluate the rate of disease control. Secondly to evaluate the duration and durability of disease response and time to disease progression. Thirdly to determine the safety of combination therapy using Bexarotene and Gemcitabine in terms of physical examination, laboratory measurements, adverse events, hospital admissions and blood / platelet transfusions. Fourthly to determine the compliance with treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or non-pregnant females aged 18 years or over 2. Histologically confirmed diagnosis of CTCL, including mycosis fungoides and Sézary syndrome. 3. Patients with CTCL stages Ib, IIa, IIb, III, IVa and IVb. Staging is to take place within 1 month of obtaining full written informed consent. 4. Patients who have failed standard skin-directed therapy and have had at least 1 course of prior systemic therapy, such as interferon, chemotherapy, Denileukin diftitox which they have either failed to respond to or have subsequently progressed. 5. Anticipated life expectancy greater than six months. 6. Written informed consent to participate in the study 7. Bexarotene naive or previous response to single-agent bexarotene, but at least 3 months since last treatment with bexarotene
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E.4 | Principal exclusion criteria |
1. ECOG Performance Status >1 2. Patients who have not received at least 1 course of prior systemic therapy for CTCL. 3. CD30+ (Ki1+ve) anaplastic large cell lymphoma 4. Patients who have failed previous treatment with bexarotene 5. Patients who have previously experienced a severe adverse reaction to bexarotene 6. Concomitant use of any anti-cancer therapy. 7. Concomitant use of any investigational agent. 8. Use of any investigational agent within 4 weeks of study entry. 9. Clinically significant active infection. 10. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. 11. Excessive alcohol consumption. To minimise the risk of pancreatitis secondary to hyperlipidaemia due to Bexarotene 12. Uncontrolled diabetes mellitus. To minimise the risk of pancreatitis secondary to hyperlipidaemia due to Bexarotene 13. Biliary tract disease. To minimise the risk of pancreatitis secondary to hyperlipidaemia due to Bexarotene 14. History of pancreatitis. To minimise the risk of pancreatitis secondary to hyperlipidaemia due to Bexarotene 15. Concomitant drug therapy with other medications that can elevate triglycerides or cause pancreatic toxicity e.g. Gemfibrozil. Due to incidence of hyperlipidaemia secondary to Bexarotene. 16. Inadequate bone marrow or other organ function, as evidenced by: Unsupported haemoglobin <9.0 g/dL (transfusions and/or erythropoietin are permitted); Absolute neutrophil count (ANC) <1.5 x 109/L; Platelet count <100 x 109/L; 17. Total bilirubin >1.25 x upper limit of normal (ULN) for institution, aspartate transaminase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/ glutamic pyruvic transaminase (ALT/SGPT) >2.0 x ULN, serum creatinine >2 x ULN for age and sex 18. Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin or cervical epithelial neoplasm [CIN1, carcinoma in situ] that has been treated curatively). 19. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures. 20. Patients who are pregnant or breast-feeding (all women of child bearing potential must use the contraceptive pill or intrauterine contraceptive device (IUCD) during the treatment period and for at least 1 month thereafter). Male patients must use a barrier method of contraception during the treatment period and for at least 1 month thereafter. 21. Any treatment for lymphoma, including photopheresis, within the 4 weeks prior to entering the study. For patients receiving long-term corticosteroid therapy, the dose should ideally be stopped and if this is not feasible reduced to as low as possible. If steroids cannot be stopped, patients who have been on stable doses less than or equal to 20mg for at least 3 months can be entered into the study. Local radiotherapy to isolated symptomatic tumour nodules requiring immediate treatment maybe given until 2 weeks prior to entering the study. 22. Warfarin |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial is to confirm the safety and efficacy of the combination of gemcitabine and bexarotene in patients whose disease is no longer controlled on skin-directed therapy alone and who have failed at least one prior systemic therapy.
The primary efficacy endpoint is the rate of objective response, defined as the proportion of patients with confirmed CR (Complete Remission), CCR (Clinical Complete Remission), or PR (Partial Remission)as determined by OPDREC (Objective Primary Disease Response Evaluation Criteria). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 19 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial will be defined as the last patient's last clinic visit in order to address the primary efficacy endpoint of 2 year PFS |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |