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

NCT01078142

Last updated date
Study Location
Universitätsmedizin Mainz
Mainz, Rheinland-Pfalz, 55131, Germany
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Follicular Lymphoma, Mantle Cell Lymphoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Follicular Lymphoma, Mantle Cell LymphomaTemsirolimus, Bendamustine and Rituximab for Relapsed Follicular Lymphoma or Mantle Cell Lymphoma
NCT01078142
  1. Mainz, Rheinland-Pfalz
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Temsirolimus, Bendamustine and Rituximab for Relapsed Follicular Lymphoma or Mantle Cell Lymphoma
Official Title  ICMJE A Phase I/II Trial to Evaluate the Safety, Feasibility and Efficacy of the Addition of Temsirolimus to a Regimen of Bendamustine and Rituximab for the Treatment of Patients With Follicular Lymphoma or Mantle Cell Lymphoma in First to Third Relapse
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.

Detailed Description

The first part of the study is a phase I study in which the maximum tolerated dose of the combination of Temsirolimus, Bendamustine and Rituximab will be established. In the phase I part of the trial 3 patients will be included in each dose level. After inclusion of 3 patients, each patient has to receive at least 2 complete cycles without DLT until the enrolment into the next cohort can be initiated. In case of one DLT, 3 additional patients will be added to the specific dose level. If a second DLT appears, the last dose level without DLT will be considered the standard dose for the phase II trial. If the third dose level is achieved without any DLT, there will be no further dose escalation.

In the phase II proportion of the trial, after establishment of a maximum tolerated dose, the efficacy of the combination regimens in two different patient cohorts will be evaluated. In the one cohort, 30 patients with relapsed mantle cell lymphoma will be treated; the second cohort will be composed of 30 patients with relapsed follicular lymphoma.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
Intervention  ICMJE Drug: Temsirolimus, Rituximab, Bendamustin

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)

Other Name: Mabthera, Rituxan, Torisel, Bendamustin, Ribomustin, Trenda
Study Arms  ICMJE Experimental: Single arm
Bendamustin, Rituximab, Temsirolimus
Intervention: Drug: Temsirolimus, Rituximab, Bendamustin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 8, 2017)
39
Original Estimated Enrollment  ICMJE
 (submitted: March 1, 2010)
72
Actual Study Completion Date  ICMJE September 8, 2017
Actual Primary Completion Date September 8, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01078142
Other Study ID Numbers  ICMJE 341
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Georg Hess, MD, Johannes Gutenberg University Mainz
Study Sponsor  ICMJE Georg Hess, MD
Collaborators  ICMJE
  • Wyeth is now a wholly owned subsidiary of Pfizer
  • Mundipharma Pte Ltd.
Investigators  ICMJE
Principal Investigator:Georg Hess, MDDepartment of Hematology, Oncology and Pneumology, Universitätsmedizin der Johannes Gutenberg-Universität, Mainz, Germany
PRS Account Johannes Gutenberg University Mainz
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP