Relapsed Refractory Mantle Cell Lymphoma MedDRA version: 14.1 Level: PT Classification code 10026801 Term: Mantle cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TORISEL 25 mg/ml concentrate and diluent for solution for infusion
Product Name: TORISEL
Product Code: PF-05208748
Pharmaceutical Form: Concentrate for solution for infusion
INN or Propose
Sponsors
Wyeth Pharmaceuticals Inc, a wholled owned subsidiary of Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 USA
Eligibility
Sex/Gender
All
Inclusion criteria
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. Refractory to or relapsed from 2 to 7 prior therapies, which may include HSCT (ie, induction + consolidation + maintenance). 4. Prior treatment with an alkylating agent and an anthracycline and rituximab, individually or in combination. 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) =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
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 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 with curative intent and are disease-free at least 2 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 / interstitial lung disease. 7. Subjects who are receiving desipramine or have an intolerance to desipramine or other tricyclic antidepressants. (this criterion pertains only to subjects who are participating in the desipramine/PK sub-study) 8. Prior treatment with TEMSR or other mTOR inhibitor. 9. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality or cardiac dysfunction that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 10. Previous history of hypersensitivity to TEMSR, its metabolites (including sirolimus), polysorbate 80, or any other components of TEMSR formulation. 11. Hypersensitivity to antihistimines or subjects who cannot receive antihistimines for other medical reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Estimate independently assessed progression free survival (PFS) in subjects with relapsed, refractory MCL.;Secondary Objective: • Estimate Overall Survival. • Estimate objective response rate, independently and investigator assessed. • Estimate investigator assessed PFS. • Assess safety, including adverse events of infection and bleeding. • 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.;Timepoint(s) of evaluation of this end point: Independentally assessed Progression Free Survival (PFS). Tumor assessments every 6-12 wks. Primary analysis approx. 69 PFS events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include PFS per the investigator assessment and ORR per independent assessment.;Timepoint(s) of evaluation of this end point: Overall survival, objective response rate, investigator assessed PFS, and safety (including AE's of infection and bleeding), affect of TEMSR to alter the disposition of Desipramine. | — |
Countries
Australia, Belgium, Bulgaria, Czech Republic, France, Germany, Hong Kong, Hungary, India, Italy, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Serbia
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc
Outcome results
None listed