Mantle Cell Lymphoma
Conditions
Keywords
Relapsed Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, Non-Hodgkins Lymphoma, Temsirolimus, Bendamustine, Phase 1/2
Brief summary
The purpose of this study is to assess the safety, tolerability and activity of the combination of bendamustine and rituximab in patients with relapsed/refractory mantle cell lymphoma who are not eligible for high dose chemotherapy and autologous/allogeneic stem cell transplantation.
Interventions
DRUGTemsirolimus
Temsirolimus 75mg i.v. day 1, 8, 15, 21 for a 28 day cycle with a maximum of 6 Cycles.
DRUGBendamustine
Bendamustin 90mg/m2 i.v. day 2 and 3 for a 28 day cycle with a maximum of 6 Cycles.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Mundipharma K.K.
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Mantle Cell Lymphoma according to REAL/WHO classification * First or second relapse or alternatively progression during therapy. Previous use of Bendamustine is permitted, if the patient has reached at least partial remission and progression occured more than 6 months after therapy. Previous high dose chemotherapy with auto-SCT is permitted, if the patient has reached at least partial remission and progression occured more than 12 months after therapy. * Patients must not be eligible for high dose chemotherapy with auto-SCT or allo-SCT. * Adequate bone marrow function (hemoglobin \> 9g/dl, platelet count \>100/nL, absolute neutrophil count \>1,5 /nL) * WHO/ECOG Performance Status 0-2 * Measurable disease (two perpendicular diameters by either physical or radiological examination) * Life expectancy ≥ 3 weeks * Written informed consent
Exclusion criteria
* Prior treatment with any m-TOR Inhibitor * Unstable or severe uncontrolled medical condition (e.g. severe congestive heart failure, myocardial infarction within the past 6 months, severe, uncontrolled arterial hypertension, renal insufficiency requiring hemodialysis, severe pulmonary disease, severe diabetes) * Abnormal liver function: transaminases or total bilirubin \> 2 x upper limit of normal (ULN) * Abnormal renal function: serum creatinine \> 2 x upper limit of normal * Previous malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. * Concurrent treatment with strong inhibitors of CYP3A4 and/or inducers of CYP3A4 * Pregnant or breastfeeding women (negative pregnancy test not older than 7 days is required for women of fertile age). Men and women of child-bearing potential must agree to use adequate contraception (i.e. failure rate \< 1% p.a. ) * Major surgery within 4 weeks before study entry; minor procedures (e.g. Implantation i.v. port catheter, Lymphnode biopsy) within 1 week before study entry * Previous therapy with any investigational agents within 28 days before study entry * Concomitant immunotherapy (e.g. Rituximab) or Chemotherapy other than Bendamustine. Use of systemic steroids should be documented and the Principal Investigator be informed. * Central nervous system (CNS) lymphomatous involvement * HIV positivity * Current or chronic hepatitis B or hepatitis C infection * Severe psychiatric illness or Individuals that are placed in an institution due to a magisterial or judiciary command. * Inability to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Dose-finding | 6 months | Is the combination of temsirolimus alongside with bendamustine at the suggested dose feasible or are dose reductions necessary. Number of dose reductions or delays of therapy due to hematologic toxicities (CTCAE) or other adverse events according to protocoll. |
| Phase II: Response Rate (Overall response rate, complete and partial response) | 6 months | What is the response rate of a therapy with temsirolimus and bendamustine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 2 years | This is defined as the period of time between the admission into the clinical trial and the progression of the lymphoma or death of any kind. |
| Safety and Tolerability of Temsirolimus and Bendamustine Combination Therapy | 2 years | Detection of overall toxicity, serious adverse events (SAE), suspected unexpected serious adverse reactions (SUSAR) during treatment with temsirolimus and bendamustine. |
Countries
Germany
Outcome results
None listed