Temsirolimus, Bendamustine and Rituximab for Relapsed Follicular Lymphoma or Mantle Cell Lymphoma

NCT01078142 | Completed Phase 1 DMC

• 1 other identifier: 341
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open label, single arm, phase I/II study. There will be no placebo usage within this trial. Phase I: Primary: To establish a maximum tolerated dose of the addition of Temsirolimus to a regimen of Bendamustine and Rituximab (BERT) in patients with relapsed follicular lymphoma and mantle cell lymphoma. Phase II: Primary: To evaluate the ORR in patients with MCL or FL treated with the established BERT dose Secondary: To determine the complete remission rate, progression free survival rate and overall survival rate and to investigate safety and tolerability of BERT.

Conditions

Follicular Lymphoma; Mantle Cell Lymphoma

Keywords

temsirolimus; bendamustine; rituximab; mantle cell lymphoma; follicular lymphoma

Outcome Measures

Primary Outcomes (1)

• Phase I: MTD / Phase II: ORR

  phase II: ORR is evaluated approx. 6 weeks after end of treatment

  Phase I: 2 months (start cycle 3), Phase II: 6 months

Secondary Outcomes (1)

• Progression free survival

  at 2 years

Study Arms (1)

Single arm

EXPERIMENTAL

Bendamustin, Rituximab, Temsirolimus

Drug: Temsirolimus, Rituximab, Bendamustin

Interventions

Temsirolimus, Rituximab, Bendamustin DRUG

Phase I: Temsirolimus 25 - 50 - 75mg, day 1,8,15 Bendamustin 90/m2, day 1,2 Rituximab 375/m2, day 1 Phase II at established dose, repeat day 28-42 (max)

Also known as: Mabthera, Rituxan, Torisel, Bendamustin, Ribomustin, Trenda

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades l, II or IIIA or mantle cell lymphoma (including Cyclin D1 expression) according to the World Health Organization classification
• Documented relapse or progression following at least one but not more than 3 antineoplastic treatments
• At least 1 measurable tumor mass (\>1.5 cm x \>1.0 cm) or bone marrow infiltration
• Subjects 18 years or older
• Status post. high dose therapy or no transplantation option available or patient refuses an aggressive treatment strategy
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
• Adequate bone marrow reserve: Platelets of at least 75000/µl, absolute neutrophil count at least 1500/µl. In case of extensive bone marrow infiltration and lower platelet or absolute neutrophil counts, patients can not be included in the phase I part of the trial. In the phase II proportion of the trial patients may be included with a platelet count of more or equal to 50000/µl on the discretion of the investigator, if thrombocytopenia is associated with massive bone marrow infiltration.
• Adequate hepatic and renal function
• Alanine aminotransferase \<2.5 x upper limit of normal (ULN); Aspartate aminotransferase \<2.5 x ULN, Total bilirubin \<1.5 x ULN
• Measured or calculated creatinine clearance \>50 mL/min
• Eastern Cooperative Oncology Group \[ECOG\] performance Status 0-2
• Female subject must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum ß-hCG pregnancy test at screening

You may not qualify if:

• Lymphoma other than MCL or FL
• Active central nervous System lymphoma. Brain MRI is required only if clinically indicated
• Pregnancy or breast feeding women
• Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia)
• Active uncontrolled infections including HIV-positivity, active Hep B or C
• Mental status precluding patient's compliance
• Comedication with strong CYP 3A4/5-inhibitors or -inducers (Appendix 22.7)
• Prior treatment with Temsirolimus
• Known CD20 negativity
• Patients refractory to Bendamustine in a prior treatment line, defined as relapse within 1 year after initiation of first cycle. Exception: termination of treatment prior to third scheduled cycle for reasons other than toxicity.
• Status post allogeneic transplantation
• Peripheral neuropathy or neuropathic pain of Grade 2 or worse
• Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for \>5 years
• Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded.
• Known intolerance to sirolimus or derivates, or Bendamustine or Rituximab.

Sponsors & Collaborators

• Georg Hess, MD: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator
• Mundipharma Pte Ltd.: collaborator

Study Sites (1)

Universitätsmedizin Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

temsirolimus; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Georg Hess, MD

  Department of Hematology, Oncology and Pneumology, Universitätsmedizin der Johannes Gutenberg-Universität, Mainz, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head Study Department Dep Hem and Oncol

Study Record Dates

• First Submitted: February 18, 2010
• First Posted: March 2, 2010
• Study Start: February 2, 2010
• Primary Completion: September 8, 2017
• Study Completion: September 8, 2017
• Last Updated: September 11, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)