A Randomized Phase 4 Study Comparing 2 Intravenous Temsirolimus (TEMSR) Regimens in Subjects With Relapsed, Refractory Mantle Cell Lymphoma

Phase 1

• Conditions: Relapsed Refractory Mantle Cell Lymphoma; MedDRA version: 12.1Level: LLTClassification code 10026801Term: Mantle cell lymphoma refractory

• Registration Number: EUCTR2009-015498-11-FR
• Lead Sponsor: Wyeth Pharmaceuticals, Inc. Acting through its division Wyeth Research, a Pfizer Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-20
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

The subject must meet all of the following criteria to be enrolled in the study:
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 HSCT (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 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 administration of TEMSR as defined by the following:
? Absolute neutrophil count (ANC) = 1,000/µL
? Platelet (PLT) =75,000/µL (= 50,000/µL 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 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

Exclusion Criteria

Presence of any of the following criteria will exclude the subject from enrollment in the study:
1. Subjects who are = 6 months from allogeneic HSCT and who are on immunosuppressive therapy or have evidence of graft host disease.
2. Prior investigational therapy within 3 weeks before 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 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.

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 progression free survival (PFS) in subjects with relapsed, refractory MCL.;Secondary Objective: Estimate Overall Survival.<br>Estimate objective response rate, 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): Progression free survival (PFS) based on blinded, independent tumor assessments will be the primary endpoint of this study.PFS is defined as the time from randomization to progressive disease or death.