A phase II study evaluating the efficacy and safety of the farnesyltransferase inhibitor ZARNESTRA® (R115777, tipifarnib) in patients with relapsed , refractory or progressive mantle cell lymphoma not appropriate for autologous bone marrow transplantation - Zarnestra® (tipifarnib) for oral administratio

• Conditions: adult patients with relapsed , refractory or progressive mantle cell lymphoma not appropriate for autologous bone marrow transplantation; MedDRA version: 9.1Level: LLTClassification code 10026801Term: Mantle cell lymphoma refractory; MedDRA version: 9.1Level: LLTClassification code 10026800Term: Mantle cell lymphoma recurrent

• Registration Number: EUCTR2006-007066-11-FR
• Lead Sponsor: GELA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-06
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Male or female subject 18 years or older.
•Initial diagnosis of histologically confirmed mantle cell lymphoma based on the World Health Organization 1997 classification.
•Patient not able to receive high dose autologous stem cell transplantation with relapsed, refractory or progressive MCL after prior anti-neoplastic treatment. Relapse or progression since previous anti-neoplastic therapy must be documented by new lesions or objective evidence of progression of existing lesions. Biopsy is not required.
•Ann Arbor stages I-IV.
•At least 1 measurable lymph node mass that is >1.5 cm in 2 perpendicular dimensions, and has not been previously irradiated or has grown since previous irradiation.
•Eastern Cooperative Oncology Group [ECOG] performance status 0-2.
•The following laboratory values at screening:
Absolute neutrophil count (ANC) >= 1.0 G/L and Platelets >= 75 G/L
Aspartate transaminase (AST) <= 2.5 x ULN; Alanine transaminase (ALT) <= 2.5 x ULN; Total bilirubin <= 1.5 x ULN; Creatinin level <= 150 µmol/L
•Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Women are neither breast feeding nor pregnant for the duration of the study. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male subject agrees to use an acceptable method for contraception for the duration of the study.
•Voluntary signed informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
•Patient with minimum life expectancy of 3 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Any other type of lymphoma.
•Previous treatment with Zarnestra®.
•Anti-neoplastic or radiation therapy within 2 weeks before Day 1 of Cycle 1.
•Major surgery within 2 weeks before Day 1 of Cycle 1.
•Rituximab, alemtuzumab (Mabcampath®), or other unconjugated therapeutic antibody within 2 weeks before Day 1 of Cycle 1
•Nitrosoureas within 2 weeks before Day 1 of Cycle 1.
•Radioimmunoconjugates or toxin immunoconjugates such as ibritumomab tiuxetan (Zevalin™), or tositumomab (Bexxar®) within 4 weeks before Day 1 of Cycle 1.
•Less than 30 days since participation in another investigational agent study on Day 1 of cycle 1. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
•Known or suspected allergy to imidazole drugs, such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole.
•Subjects not adequately recovered from any treatment-related non hematologic toxicity (recovery is defined as NCI CTC v3.0 Grade 0 or 1).
•Symptomatic peripheral neuropathy of any grade.
•Diagnosed or treated for a malignancy other than NHL within 5 years before Day 1 of Cycle 1, with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy. Subjects previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score <=7, and a prostate specific antigen (PSA) <=10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (ie, prostatectomy or radiotherapy) >= 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy.
•Active systemic infection requiring treatment.
•Previously known HIV positive serology
•Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
•Adult patient under guardian.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To measure efficacy by evaluation of the overall response rate (complete response [CR] + complete response unconfirmed [CRu] + partial response [PR]) to Zarnestra as single agent, according to criteria based on those developed by Cheson at al;Secondary Objective: •To determine the overall CR rate (CR + CRu)<br>•To determine progression-free survival (PFS) <br>•To determine overall survival<br>•To evaluate the safety and tolerability of Zarnestra® <br>;Primary end point(s): Efficacy measured by evaluation of the overall response rate (complete response [CR] + complete response unconfirmed [CRu] + partial response [PR]) to Zarnestra® as single agent, according to criteria based on those developed by Cheson at al.