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

Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01170052
• Other study ID #: EudraCT-No.: 2009-014844-13
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: July 14, 2010
• Last updated: March 15, 2011
• Start date: May 2010
• Est. completion date: April 2014

Study information

• Verified date: June 2010
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 20
• Est. completion date: April 2014
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma

Intervention

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

Locations

Country	Name	City	State
Germany	Dept. of Hematology and Oncology, Charité, Campus Benjamin Franklin	Berlin
Germany	Dept. of Hematology and Oncology, Charité, Campus Charité Mitte	Berlin
Germany	Dept. of Hematology and Oncology, Charité, Campus Virchow Klinikum Charité	Berlin

Sponsors (3)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Mundipharma K.K., Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	No
Secondary	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	No
Secondary	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	Yes