A Randomized Phase 4 Study Comparing 2 Intravenous Temsirolimus (TEMSR) Regimens in Subjects With Relapsed, Refractory Mantle Cell Lymphoma - ND
- Conditions
- Relapsed Refractory Mantle Cell LymphomaMedDRA version: 9.1Level: LLTClassification code 10026801
- Registration Number
- EUCTR2009-015498-11-IT
- Lead Sponsor
- Wyeth Pharmaceuticals, Inc. Acting through its division Wyeth Research, a Pfizer Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1.MCL confirmed locally with histology, immunophenotype, and cyclin D1 analysis.
2.Male or female subjects aged 18 years or older.
3.Received 2 to 7 prior therapies, which may include hematopoietic stem cell transplant (ie, induction + consolidation + maintenance).
4.Prior treatment with an alkylating agent and an anthracycline, rituximab, individually or in combination, and status that is at least 1 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.
5.Measurable disease (as described in Section 19.1) in an area of no prior radiotherapy or clear progression in an area that was previously irradiated
6.Adequate organ and marrow function obtained within 2 weeks prior to first dose of TEMSR as defined by the following:
•Absolute neutrophil count (ANC) = 1000/?L
•Platelet (PLT) ? 75,000/?L (= 50,000/?L is allowed if with bone marrow involvement)
•Hemoglobin ? 8 g/dL
•Total bilirubin = 1.5 x upper limit normal (ULN) (if abnormal, direct bilirubin must be = 1.5 x ULN)
•Aspartate aminotransferase (AST) = 3 x ULN (= 5 x ULN is allowed if with liver involvement)
•Serum creatinine = 2 x ULN
•Fasting serum cholesterol = 350 mg/dL (9.01 mmol/L)
•Triglycerides = 400 mg/dL (4.5 mmol/L)
•Glycosylated hemoglobin (Hgb A1c) ? 10% (optimal therapy permitted)
•Other laboratory values all common toxicity criteria (CTC) version 3.0 grade = 2 unless related to lymphomatous organ involvement.
7.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
8.For women of child bearing potential, a negative serum pregnancy test prior to the first dose administration of any test article (ie, Desipramine and/or TEMSR). For women and men who are not surgically sterile or postmenopausal, willingness to use a medically acceptable form of birth control (ie, condoms with spermicide, contraceptives, etc.) during treatment and for 12 weeks after the last dose administration of TEMSR.
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
1.Subjects who are = 6 months from allogeneic hematopoietic stem cell transplant and who are on immunosuppressive therapy or have evidence of graft host disease.
2.Prior investigational therapy within 3 weeks before administration of the first infusion of TEMSR. Investigational therapy is defined as treatment that is not approved for any indication.
3.Treatment within the following time frame relative to first dose administration of TEMSR:
•Chemotherapy, radiotherapy, immunotherapy, or major surgery = 3 weeks
•Nitrosourea or mitomycin = 6 weeks
•Radioimmunotherapy = 8 weeks
•Other nonmyelosuppressive biological response modifiers ? 2 weeks.
4.Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible as long as they are clinically stable for = 2 months prior to first dose administration of TEMSR (no significant changes in anticonvulsant doses, mental status, or clinical symptoms related to CNS metastases) after completion of definitive therapy.
5.Current active second malignancy other than nonmelanoma skin cancers and clinically localized prostate cancer. Subjects are not considered to have a currently active malignancy if they have completed anti cancer therapy and are disease-free at least 5 years prior to the first dose administration of TEMSR. Subjects with a history of cervical carcinoma in situ, breast ductal carcinoma in situ, or breast lobular carcinoma in situ are considered eligible provided they have completed definitive therapy.
6.Any prior history of noninfectious interstitial pneumonitis.
7.Subjects who are receiving desipramine or have an intolerance to desipramine or other tricyclic antidepressants.
8.Prior treatment with TEMSR or other mTOR inhibitor.
9.Evidence of significant medical illness or abnormal laboratory finding that in the opinion of the investigator would substantially increase the risk associated with the subject’s participation in the study or impact the assessment of safety and/or efficacy. Examples include, but are not limited to: ongoing or active infection, significant uncontrolled cardiac disease such as congestive heart failure, myocardial infarction within past 6 months, angina requiring treatment, or other clinically significant or uncontrolled conditions.
10.Previous history of hypersensitivity to TEMSR, its metabolites (including sirolimus), polysorbate 80, or any other components of TEMSR formulation;
11.Hypersensitivity to antihistamines or subjects who cannot receive antihistamines for other medical reasons.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Estimate independently assessed PFS in subjects with relapsed or refractory MCL.;Secondary Objective: •Estimate OS.<br>•Estimate objective response rate (ORR), independently and investigator assessed.<br>•Estimate investigator assessed PFS.<br>•Assess safety, including adverse events of infection and bleeding.<br>•Quantify the potential effect of TEMSR to alter the disposition of desipramine, a substrate of CYP2D6 metabolism.;Primary end point(s): PFS based on blinded, independent tumor assessments will be the primary endpoint of this study. An independent radiology vendor will be used to derive this endpoint.
- Secondary Outcome Measures
Name Time Method