Patients with relapsed mantle cell and folicular lymphoma requiring treatment. A novel combination regimene is evaluated to evaluate the safety and feasibility (phase I) and the efficacy of an established regimen (bendamustin - rituximab) and the additional use of the inihibitor of the mammalian target of rapamycin temsirolimus.
Conditions
Interventions
Trade Name: Torisel
Product Name: Torisel
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: TEMSIROLIMUS
CAS Number: 162635-04-3
Concentration unit: mg mill
Sponsors
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades l, II or IIIA or mantle cell lymphoma (including Cyclin D1 expression) according to the World Health Organization classification • Documented relapse or progression following at least one but not more than 3 antineoplastic treatments • At least 1 measurable tumor mass (>1.5 cm x >1.0 cm) or bone marrow infiltration • subjects 18 years or older • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study • Adequate bone marrow reserve: Platelets of at least 75000/µl, absolute neutrophil count at least 1500/µl. In case of extensive bone marrow infiltration and lower platelet or absolute neutrophil counts, patients can not be included in the phase I part of the trial. In the phase II proportion of the trial patients may be included with a platelet count of more or equal to 50000/µl on the discretion of the investigator, if thrombocytopenia is associated with massive bone marrow infiltration. • adequate hepatic and renal function o Alanine aminotransferase 50 mL/min • Eastern Cooperative Oncology Group [ECOG] performance Status 0-2 • Female subject must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum ß-hCG pregnancy test at screening 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
Exclusion criteria: • Lymphoma other than MCL or FL • Active central nervous System lymphoma. Brain MRI is required only if clinically indicated • pregnancy or breast feeding women • severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia) • active uncontrolled infections including HIV-positivity, active Hep B or C • mental status precluding patient’s compliance • Comedication with strong CYP 3A4/5-inhibitors or –inducers (Appendix 22.7) • Prior treatment with Temsirolimus • Known CD20 negativity • Patients refractory to Bendamustine in a prior treatment line, defined as relapse within 1 year after initiation of first cycle. Exception: termination of treatment prior to third scheduled cycle for reasons other than toxicity. • Status post allogeneic transplantation • Peripheral neuropathy or neuropathic pain of Grade 2 or worse • Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for >5 years • Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded. • Known intolerance to sirolimus or derivates, or Bendamustine or Rituximab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: safety and feasibility - phase I objective response rate - phase II;Secondary Objective: To determine the complete remission rate, progression free survival rate and overall survival rate and to investigate safety and tolerability of BERT;Primary end point(s): The primary objective of the phase I part of the trial is The determination of a maximum tolerated dose of the addition of Temsirolimus to a combination of Bendamustine and Rituximab (BERT) The primary objective of the phase II part of the trial is The determination of the objective response rate (number of patients with PR and CR) in patients with relapsed mantle cell or follicular lymphoma treated at the maximum tolerated dose of BERT. | — |
Countries
Germany
Outcome results
None listed