An Open-label, Randomized, Phase 3 Trial of intravenous Temsirolimus (CCI-779) at two Dose Levels Compared to Investigator's Choice Therapy in relapsed, Refractory Subjects with Mantle Cell lymphoma (MCL)

• Conditions: Mantle Cell Lymphoma; MedDRA version: 8.1Level: LLTClassification code 10061275Term: Mantle cell lymphoma

• Registration Number: EUCTR2004-001430-16-DE
• Lead Sponsor: Wyeth Research, Division of Wyeth Pharmaceuticals, Inc. (A Pfizer Company)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-09-22
• Last Update Posted: 26 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 177

Inclusion Criteria

1.Mantle Cell Lymphoma (MCL) confirmed with histology, immunophenotype, and cyclin D1 analysis.
2.Received 2 to 7 prior therapies which may include hematopoietic stem cell transplant (i.e. induction + consolidation + maintenance).
3.Prior treatment with an alkylating agent and an anthracycline, rituximab, individually or in combination, and status that is at least one of the following: ·Primary disease refractory to at least 2 regimens·Refractory to at least 1 regimen after first relapse·Refractory or untreated after second or greater relapse·Refractory to first line and relapsed after second line. Chemotherapy combinations may include, but are not limited to: CHOP, R-CHOP, FCM, R-FCM, ICE, DHAP, and hyper-CVAD.
4.Measurable disease in an area of no prior radiation therapy or clear progression in an area that was previously irradiated, with a lymph node or tumor mass = 1.5 cm x 1.5 cm by CT.
5.Adequate organ and marrow function obtained = 2 weeks prior to first dose of test article as defined by:·ANC = 1,000/uL·PLT =75,000/uL ( =50,000/uL acceptable if bone marrow involved)·Hgb =8 g/dL·Total bilirubin =1.5 x ULN (if abnormal, direct bilirubin = 1.5 x ULN)·AST =3 x ULN (=5 x ULN if liver involvement with MCL)·Serum creatinine =2 x ULN·Fasting serum cholesterol =350 mg/dL (9.04 mmol/L)·Triglycerides =400 mg/dL (4.5 mmol/L)·Other laboratory values all CTC version 3.0 Grade =2 unless related to lymphomatous organ involvement
6.Karnofsky Performance Status (KPS) =60% (corresponds to ECOG Performance Status 0 to 2).
7.Age =18 years.
8.Life expectancy =3 months.
9.For women of childbearing potential, a negative serum pregnancy test result within 1 week before the first dose. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
10.Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use medically acceptable methods of birth control (e.g. cervical cap, diaphragm with spermicide, condoms with spermicide, or intra uterine device) for the duration of the study and for 12 weeks after the last dose.
11.Signed and dated institutional review board/ethics committee-approved informed consent before any protocol specific screening procedures are performed.

Inclusion Criteria Subjects Crossing over to Treatment with 175/75 mg Temsirolimus.

1. Adequate organ and marrow function obtained = 2 weeks prior to first dose 175/75 mg or 75 mg as defined by:
ANC = 1,000/uL·
PLT = 75,000/uL (³ 50,000/uL acceptable if bone marrow involved)
Hgb = 8 g/dL·
Total bilirubin =1.5 x ULN (if abnormal, direct bilirubin = 1.5 x ULN)·
AST = 3 x ULN (= 5 x ULN if liver involvement with MCL)·
Serum creatinine = 2 x ULN·
Fasting serum cholesterol = 350 mg/dL (9.04 mmol/L)·
Triglycerides = 400 mg/dL (4.5 mmol/L)
Other laboratory values all CTC version 3.0 Grade =2 unless related to lymphomatous organ involvement
2. Performance Status (KPS) = 60% (corresponds to ECOG Performance Status 0 to 2)
3. For those subjects previously or currently treated with temsirolimus, recovery of related toxicities to grade 0-baseline and/or within protocol required laboratory values required for treatment.
4. For women of childbearing potential, a negative serum pregnancy test result within 1 week before the first dose (only applicable to subjects who have previousl

Exclusion Criteria

1.Subjects who are less than or equal to 6 months from allogeneic hematopoietic stem cell transplant and who are on immunosuppressive therapy or have evidence of graft versus host disease.
2.Prior investigational therapy within 3 weeks of first dose. Investigational therapy is defined as treatment that is not approved for any indication.
3.Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. (Treated CNS metastases must be stable for > 2 weeks prior to Day 1.)
4.Active second malignancy that requires treatment or that would interfere with assessment of response of MCL.
5.History of any other primary malignancy with < 5 years documentation of a disease-free state. (May be discussed with Wyeth medical monitor, e.g. subjects with a history of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ, which have been successfully treated, are not excluded.)
6.Treatment with the following within the timeframe specified prior to the first dose:·Chemotherapy, radiotherapy, immunotherapy or major surgery = 3 weeks·Nitrosourea, or mitomycin = 6 weeks·Radioimmunotherapy = 8 weeks·Other non-myelosuppressive biologic response modifiers < 2 weeks
7.Uncontrolled current illness including, but not limited to:·Ongoing or active infection·Symptomatic congestive heart failure·Unstable angina pectoris (myocardial infarction within 6 months of Day 1)·Clinically significant cardiac arrhythmia·Known pulmonary hypertension
8.Immunocompromised subjects, including subjects known to be human immunodeficiency virus (HIV) positive and/or acute or chronic hepatitis (HbsAg) positive or hepatitis C virus (anti-HCV) positive. Subjects that are immunocompromised due to MCL disease only are not excluded.
9.Known hypersensitivity to any of the components in temsirolimus.
10.Female subjects who are breast-feeding.
11.Any significant medical or illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the subject’s risk by participating in this study.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Progression-Free Survival (PFS);Secondary Objective: Safety and Tolerability, Objective Response Rate (CR + CRu +PR), Overall Survival (OS);Primary end point(s): The primary efficacy endpoint of this study is a comparison of the Progression free survival of subjects treated with temsirolimus 175 mg for three administrations every week followed by 75 mg weekly or temsirolimus 175 mg for three administrations every week followed by 25 mg weekly or investigator’s choice (single agent)