Bendamustine and Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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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.

Official Title
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Phase I/II Study With Bendamustine and Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Non-hodgkin's Lymphoma (NHL) Not Eligible for High Dose Chemotherapy and Autologous/Allogeneic Stem Cell Transplantation

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Temsirolimus
* Drug: Bendamustine
* Drug: Temsirolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Temsirolimus|Temsirolimus 75mg i.v. day 1, 8, 15, 21 for a 28 day cycle with a maximum of 6 Cycles.|
|Drug: Bendamustine|Bendamustin 90mg/m2 i.v. day 2 and 3 for a 28 day cycle with a maximum of 6 Cycles.|
|Drug: Temsirolimus|Consolidation Therapy for Patients reached CR or PR with Temsirolimus 75mg weekly until progression.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Dose-finding | 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. | 6 months | 
| Phase II: Response Rate (Overall response rate, complete and partial response) | What is the response rate of a therapy with temsirolimus and bendamustine. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | 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. | 2 years | 
| Safety and Tolerability of Temsirolimus and Bendamustine Combination Therapy | Detection of overall toxicity, serious adverse events (SAE), suspected unexpected serious adverse reactions (SUSAR) during treatment with temsirolimus and bendamustine. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, Non-Hodgkins Lymphoma, Temsirolimus, Bendamustine, Phase 1/2