Diffuse large B-cell lymphoma with documented relapse or progression following at least one but a maximum of two prior treatments, aged older than 18 years MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004943
Conditions
Interventions
Trade Name: Torisel® 30 mg Konzentrat und Verdünnungsmittel zur Herstellung einer Infusionslösung
Product Name: Torisel®
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or P
Sponsors
Ruprecht-Karls University Heidelberg, Medical Faculty
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: · Patients with histologically proven diagnosis of diffuse large cell B-cell lymphoma (DLBCL) according to the World Health Organization classification · Documented relapse or progression following at least one treatment but a maximum of 2 prior treatments. Prior treatment must have included at least 3 cycles of anthracycline containing chemotherapy (e.g. CHOP-like). · Any of the following: at least 1 measurable tumor mass (>1.5 cm x >1.0 cm), involvement of any organ 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, Hemoglobin of at least 10g/dl · Alanine aminotransferase (ALT) 70 mL/min · Eastern Cooperative Oncology Group [ECOG] performance Status =65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: · Active central nervous System lymphoma. Brain MRI is required only if clinically indicated · Pregnancy or breast feeding women · Lymphoma other than DLBCL · 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 · Prior treatment with Temsirolimus · Known CD20 negativity · Patients refractory to DHAP in a prior treatment line · Prior autologous or allogeneic stem cell or bone marrow 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 during the conduct of the trial. Concurrent participation in non-treatment studies is not excluded. · Known intolerance to Dexamethasone, Sirolimus or derivates, Cytarabine, Cisplatine or Rituximab. Known intolerance to any other ingredients contained in the trial therapy. Known intolerance to pre-treatment or premedication in this trial (e.g. Prednisolone, Allopurinol, H1-Blocker, Paracetamole).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The STORM-trial consists of two parts. In the part I (dose escalation of Temsirolimus) the primary objective is to establish a maximum tolerated dose of Temsirolimus in combination with Rituximab and DHAP. In the part II (full target dose) the primary objective is to evaluate the ORR in patients with relapsed DLBCL. ;Secondary Objective: The STORM-trial consists of two parts. In the part I (dose escalation of Temsirolimus) the secondary objective is to prove ability to mobilize stem cells in patients scheduled to high dose therapy. In the part II (full target dose) the secondary objective is to evaluate PFS, OS and Toxicity.;Primary end point(s): Part I (dose escalation of Temsirolimus): establish a maximum tolerated dose of Temsirolimus in combination with Rituximab and DHAP. part II (full target dose): ORR in patients with relapsed DLBCL. ;Timepoint(s) of evaluation of this end point: Part I: 4 cohorts, 6 patients will be included in each dose level, administering up to a maximum of 4 cycles 25 mg, 50 mg, 75mg or 100mg Temsirolimus in combination with Rituximab and DHAP. Part II: Active treatment with Temsirolimus in combination with R-DHAP for 2 to 4 cycles will last approximately to a maximum of 12 weeks. Patients will be followed for disease progression and or death and initiation of subsequent therapy for DLBCL for at least 2 years (if no event occurs) up to a maximum of 5 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part I: Stem cell mobilization Part II: PFS, OS and Toxicity;Timepoint(s) of evaluation of this end point: Part I: Stem cell mobilization is recommended after the second treatment cycle with G-CSF starting on day 5. Part II: Active treatment with Temsirolimus in combination with R-DHAP for 2 to 4 cycles will last approximately to a maximum of 12 weeks. Patients will be followed for disease progression and or death and initiation of subsequent therapy for DLBCL for at least 2 years (if no event occurs) up to a maximum of 5 years. | — |
Countries
Germany
Contacts
Public ContactJulia Meißner
Ruprecht-Karls University Heidelberg, Medical Faculty
Outcome results
None listed