Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma

A RANDOMIZED PHASE 4 STUDY COMPARING 2 INTRAVENOUS TEMSIROLIMUS (TEMSR) REGIMENS IN SUBJECTS WITH RELAPSED, REFRACTORY MANTLE CELL LYMPHOMA

This study will compare the effectiveness and safety of two different doses of temsirolimus (Torisel).

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: temsirolimus; Drug: temsirolimus

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Czechia
  • Praha 10, Czechia, 100 34
    • Fakultní nemocnice Královské Vinohrady
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
  • Czech Republic
    • Praha 10, Czech Republic, Czechia, 10034
      • Fakultní nemocnice Královské Vinohrady
• France
  • Vandoeuvre les Nancy, France, 54500
    • CHU de Nancy
• Germany
  • Aachen, Germany, 52074
    • Klinik fuer Onkologie und Haematologie, Medizinische Klinik IV
  • Mainz, Germany, 55131
    • Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik
• Italy
  • Catania, Italy, 95124
    • Presidio Ferrarotto - A.O.U. - PoliclinicoVittorio Emanuele
  • Modena, Italy, 41124
    • Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
  • Torino, Italy, 10126
    • Struttura Complessa di Ematologia, Dipartimento di Oncologia ed Ematologia-
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University
• Poland
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
• Romania
  • Bucuresti, Romania, 030171
    • Spitalul Clinic Coltea, Clinica de Hematologie
  • Bucuresti, Romania, 022328
    • Institutul Clinic Fundeni Bucuresti, Sectia II Hematologie
  • Bucuresti, Romania, 050098
    • Spitalul Universitar de Urgenta Bucuresti, Clinica de Hematologie
• Russian Federation
  • Kazan, Russian Federation, 420029
    • Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republic
  • Saint-Petersburg, Russian Federation, 197022
    • GBOU VPO "First Saint-Petersburg State Medical University n.a. I.P.Pavlov"
  • Saint-Petersburg, Russian Federation, 197022
    • Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia,Clinic for Hematology
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina
• United States
  • Florida
    • Miami, Florida, United States, 33133
      • Mercy Research Institute
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Veterans Affairs New Jersey Healthcare System-Hematology/Oncology Section (111)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Clinic Oklahoma Communities dba Mercy Clinic Oncology/Hematology-McAuley
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City-Oncology Infusion
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System
    • Seattle, Washington, United States, 98108
      • Amy Shen, RPh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have confirmed mantle cell lymphoma diagnosis.
• Have measurable disease.
• Have received at least 2 prior treatment, which may include stem cell transplant.
• Have adequate organ and bone marrow function.
• There are other criteria--please discuss with your doctor.

Exclusion Criteria:

• Had any prior treatment with temsirolimus or mTOR inhibitor.
• Had allogeneic stem cell transplant within last 6 months and on immunosuppressive therapy.
• Has active or untreated brain or central nervous system metastases.
• There are other criteria--please discuss with your doctor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: temsirolimus (Torisel) 175mg weekly x 3, then 75mg weekly	Drug: temsirolimus; 175mg IV once a week for first 3 weeks, followed by 75mg IV once a week until disease progression, provided that patient is tolerating treatment and getting clinical benefit; Other Names: Torisel; Drug: temsirolimus; 75mg IV once a week until until disease progression, provided that patient is tolerating treatment and getting clinical benefit; Other Names: Torisel
Active Comparator: temsirolimus (Torisel) 75mg weekly	Drug: temsirolimus; 175mg IV once a week for first 3 weeks, followed by 75mg IV once a week until disease progression, provided that patient is tolerating treatment and getting clinical benefit; Other Names: Torisel; Drug: temsirolimus; 75mg IV once a week until until disease progression, provided that patient is tolerating treatment and getting clinical benefit; Other Names: Torisel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Independently Assessed Progression-free Survival (PFS)	PFS is defined as the time from randomization to first documentation of disease progression by the independent assessor or to death due to any cause, whichever occurred first. PFS = (earliest date of progression or death due to any cause- randomization date+1)/30.4. PFS assessment was done using EMA guidelines for sensitivity analysis censoring. Participants who were alive and progression-free at the time of analysis were censored on the date of last assessment; participants without adequate baseline assessment or without post-baseline assessments were censored on the randomization date; participants who died or progressed after 2 or more missed visits were censored on the date of last tumor assessment prior to the missing visit; and participants who started new anti-cancer therapy prior to death or progression were censored on the date of last tumor assessment prior to the start of anti-tumor treatment.	From randomization date to the date of first documentation of progression or death (average follow up done for 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	From randomization date until death due to any cause (average follow up done for 56.1 months)
Independent Assessment - Objective Response Rate (ORR = CR + PR)	ORR is defined as the percentage of participants with confirmed CR or PR according to the Cheson Criteria relative to all randomized Participants. Tumor responses were determined using information from objective measurements from computed tomography information including B-symptom evaluation, physical examination, ECOG performance status, assessment of liver and spleen, laboratory assessments such as bone marrow biopsies and/or aspirates, biochemical markers of disease activity and hematology results. Participants who did not have on-study radiographic tumor re-evaluation or who died, progressed or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the (CT) scans, as well as clinical assessment of ORR.	From randomization date until end of treatment (average follow up done for 15 months)
Investigator's Assessment ORR (ORR = CR + PR)	ORR is defined as the percentage of participants with confirmed CR or PR according to the Cheson Criteria relative to all randomized Participants. Tumor responses were determined using information from objective measurements from computed tomography information including B-symptom evaluation, physical examination, ECOG performance status, assessment of liver and spleen, laboratory assessments such as bone marrow biopsies and/or aspirates, biochemical markers of disease activity and hematology results. Participants who did not have on-study radiographic tumor re-evaluation or who died, progressed or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the (CT) scans, as well as clinical assessment of ORR.	From randomization date until end of treatment (average follow up done for 15 months)
Investigator Assessed PFS	PFS is defined as the time from randomization to first documentation of disease progression by the independent assessor or to death due to any cause, whichever occurred first. PFS = (earliest date of progression or death due to any cause- randomization date+1)/30.4. PFS assessment was done using EMA guidelines for sensitivity analysis censoring. Participants who were alive and progression-free at the time of analysis were censored on the date of last assessment; participants without adequate baseline assessment or without post-baseline assessments were censored on the randomization date; participants who died or progressed after 2 or more missed visits were censored on the date of last tumor assessment prior to the missing visit; and participants who started new anti-cancer therapy prior to death or progression were censored on the date of last tumor assessment prior to the start of anti-tumor treatment.	From randomization date to the date of first documentation of progression or death (average follow up done for 15 months)
Percentage of Participants With Treatment-Emergent Infection- Related Adverse Events (AEs) With Grade 2 or Higher as Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)	An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Treatment emergent adverse event=as an event that emerged during treatment period that was absent before treatment, or worsened during treatment period relative to pretreatment state. Treatment-emergent infection-related AEs included events: pneumonia, bronchitis, infection, herpes simplex, oral candidiasis and sepsis. Grading by NCI CTCAE Version 3.0.: Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening; urgent intervention indicated; Grade 5= death.	From screening up to a maximum of 57.1 months
Percentage of Participants With Treatment-Emergent Bleeding-Related AEs With Grade 2 or Higher as Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)	An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Treatment emergent adverse event=as an event that emerged during treatment period that was absent before treatment, or worsened during treatment period relative to pretreatment state. Treatment-emergent bleeding related AEs included events: epistaxis and ecchymosis. AE were assessed according to maximum severity grading based on NCI CTCAE Version 4.03.Grade 1=mild; Grade 2=moderate; within normal limits. Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening or disabling; urgent intervention indicated; Grade 5=death.	From screening up to a maximum of 57.1 months
Quantify the Potential Effect of TEMSR on AUC and Cmax	Potential TEMSR effects were investigated by calculating the ratio of AUCs with and without concomitant TEMSR from the model-estimated effect of TEMSR on apparent clearance (CL/F) values and using individual ratios of observed Cmax values with and without concomitant temsirolimus, for both parent and metabolite. The AUC mean ratio was calculated as 1 / mean shift on apparent clearance from TEMSR, and the 90% CI of the AUC ratios was calculated as 1 / 90% CI of the shift on apparent clearance from TEMSR. AUC: Area under plasma concentration-time curve from time zero to infinity Cmax: Characterization of maximum observed plasma concentration	From one week predose (Day -7, -4hr, -8hr, -48hr) upto 2 weeks post dose (4hr, 8hr, 48hr and Day 8)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: August 10, 2010
• First Posted (Estimate): August 11, 2010

Study Record Updates

• Last Update Posted (Actual): May 20, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: temsirolimus; Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 3066K1-4438; B1771007 (Other Identifier: Alias Study Number); 2009-015498-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.