Strategies to prolong remission duration in elderly patients with MCL are urgently needed. The effects of Rapamycin derivates on MCL cells in vitro and the evolving in vivo data support the further investigation of RAD001 in this incurable disease
Conditions
Interventions
Trade Name: Afinitor
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Concentration unit: mg milligram(s)
Concentration
Sponsors
Technical University of Munich
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with a proven history of mantle cell lymphoma 2. Patients with achieved disease control after one to four lines of chemotherapy (complete response, partial response, stable disease) for mantle cell lymphoma. 3. Patients must have been treated with a CHOP-like chemotherapy or a Fludarabine-containing regimen previously and Rituximab must have been used as part of the previous treatment. 4. Age = 60 years or patients =40 and 9 g/dL 8. Adequate liver function as shown by: serum bilirubin = 1.5 xupper limit of normal (ULN), and serum transaminases activity = 3 x ULN. With the exception of serum transaminases (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Prior treatment with any investigational drug within the preceding 4 weeks 2. Chronic treatment with systemic steroids or another immunosuppressive agent except for Rituximab. 3. Uncontrolled brain or leptomeningeal disease manifestation, including patients who continue to require glucocorticoids for brain or leptomeningeal disease manifestation 4. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. 5. Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration, psychiatric disease) 6. A known history of HIV seropositivity 7. History or serology indicating active or chronic Hepatitis B or C or detection of viral DNA (Hep. B or C) via PCR 8. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of EVEROLIMUS (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) 9. Patients with an active, bleeding diathesis or on oral antivitamin K medication (except low dose coumarin) 10. Previous organ transplantation. 11. Women who are pregnant or breast feeding, or women able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of EVEROLIMUS). Oral, implantable, orinjectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. A highly effective methode of birth control is defined as those which results in a low failure rate (i.e. less than 1% per year) for example sexual abstinence or vasectomised partner. 12. Patients who have received prior treatment with an mTor inhibitor. 13. History of noncompliance to medical regimens 14. Patients unwilling to or unable to comply with the protocol 15. Patients with galactose intolerance, lack of lactase or malabsorption of glucose or galactose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy (time to progression) and safety of a maintenance therapy with Everolimus in patients with MCL aged over 60 years or aged over 40 years but who are not eligible for high dose chemotherapy followed by autologous stem cell support or allogeneic stem cell transplantation;Secondary Objective: ;Primary end point(s): Time to progression despite maintenance therapy with everolimus. Start of measurement is defined as last day of application of remission-inducing chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To analyze toxicity and feasibility of a treatment with EVEROLIMUS in patients with MCL after first, second, third and fourth line chemotherapy • To analyze surrogate parameters involved in angiogenesis and cell-cycle regulation in patients with circulating MCL cells or bone marrow involvement (only in patients with circulating MCL cells or with bone marrow involvement) • To compare the duration of previous responses with the duration of responses in patients with maintenance therapy. • To analyze the conversion rate in MCL patients during maintenance therapy (improvement of partial to complete response, stable disease to partial or complete response). • To analyze the overall survival of patients with maintenance therapy. • To analyze Quality of life during maintenance therapy | — |
Countries
Germany
Contacts
Public ContactUlrich Keller
Klinikum rechts der Isar der Technischen Universität München
Outcome results
None listed