Phase II study of the mTOR-Inhibitor EVEROLIMUS asmaintenance therapy in patients aged over 60 years with MantleCell Lymphoma (MCL) after first, second, third or fourth linechemotherapyNew title since Protocol Version 4.0Phase II study of the mTOR-Inhibitor EVEROLIMUS asmaintenance therapy in patients aged over 60 years with MantleCell Lymphoma (MCL) after first, second, third or fourth linechemotherapy - CRAD001C2428
- Conditions
- 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
- Registration Number
- EUCTR2007-005116-12-DE
- Lead Sponsor
- Technical University of Munich
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
- 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 <60 years of age who are
not eligible for high dose chemotherapy followed by
autologous stem cell support or allogeneic stem cell
transplantation.
5. Minimum of two weeks since any major surgery, completion
of radiation, or completion of all prior systemic anticancer
therapy (adequately recovered from the acute toxicities of
any prior therapy).
6. WHO performance status = 2
Adequate bone marrow function as shown by: ANC = 1.5 x
109/L, Platelets = 100 x 109/L, Hgb > 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 (< 5 x ULN) if the patient has liver metastases
9. Life expectancy of at least 3 months
10. Signed informed consent
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
- 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the efficacy (time to progression) and safety of a<br>maintenance therapy with Everolimus in patients with MCL aged<br>over 60 years or aged over 40 years but who are not eligible for high<br>dose chemotherapy followed by autologous stem cell support or<br>allogeneic stem cell transplantation;Secondary Objective: ;Primary end point(s): Time to progression despite maintenance therapy with everolimus.<br>Start of measurement is defined as last day of application of remission-inducing chemotherapy.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): To analyze toxicity and feasibility of a treatment with<br>EVEROLIMUS in patients with MCL after first, second,<br>third and fourth line chemotherapy<br>• To analyze surrogate parameters involved in angiogenesis<br>and cell-cycle regulation in patients with circulating MCL<br>cells or bone marrow involvement (only in patients<br>with circulating MCL cells or with bone marrow<br>involvement)<br>• To compare the duration of previous responses with the<br>duration of responses in patients with maintenance therapy.<br>• To analyze the conversion rate in MCL patients during<br>maintenance therapy (improvement of partial to complete<br>response, stable disease to partial or complete response).<br>• To analyze the overall survival of patients with maintenance<br>therapy.<br>• To analyze Quality of life during maintenance therapy