Back to resultsComparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
Primary Purpose
Non-Hodgkin's Lymphoma
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
temsirolimus
temsirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma, temsirolimus
Eligibility Criteria
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.
Sites / Locations
- Mercy Research Institute
- Veterans Affairs New Jersey Healthcare System-Hematology/Oncology Section (111)
- Mercy Clinic Oklahoma Communities dba Mercy Clinic Oncology/Hematology-McAuley
- Mercy Hospital Oklahoma City-Oncology Infusion
- Amy Shen, RPh
- VA Puget Sound Health Care System
- St George Hospital
- Royal Adelaide Hospital
- Royal Hobart Hospital
- Box Hill Hospital
- The Alfred Hospital
- Fakultni nemocnice Kralovske Vinohrady
- Fakultni nemocnice Kralovske Vinohrady
- Vseobecna fakultni nemocnice v Praze
- CHU de Nancy
- Klinik fuer Onkologie und Haematologie, Medizinische Klinik IV
- Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik
- Presidio Ferrarotto - A.O.U. - PoliclinicoVittorio Emanuele
- Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
- Struttura Complessa di Ematologia, Dipartimento di Oncologia ed Ematologia-
- Severance Hospital, Yonsei University
- Samsung Medical Center
- Malopolskie Centrum Medyczne S.C.
- Institutul Clinic Fundeni Bucuresti, Sectia II Hematologie
- Spitalul Clinic Coltea, Clinica de Hematologie
- Spitalul Universitar de Urgenta Bucuresti, Clinica de Hematologie
- Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republic
- GBOU VPO "First Saint-Petersburg State Medical University n.a. I.P.Pavlov"
- Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva
- Clinical Centre of Serbia,Clinic for Hematology
- Oncology Institute of Vojvodina
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
temsirolimus (Torisel) 175mg weekly x 3, then 75mg weekly
temsirolimus (Torisel) 75mg weekly
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause.
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.
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.
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01180049
Brief Title
Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
Official Title
A RANDOMIZED PHASE 4 STUDY COMPARING 2 INTRAVENOUS TEMSIROLIMUS (TEMSR) REGIMENS IN SUBJECTS WITH RELAPSED, REFRACTORY MANTLE CELL LYMPHOMA
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2011 (Actual)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
June 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will compare the effectiveness and safety of two different doses of temsirolimus (Torisel).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma
Keywords
Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma, temsirolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
101 (Actual)
8. Arms, Groups, and Interventions
Arm Title
temsirolimus (Torisel) 175mg weekly x 3, then 75mg weekly
Arm Type
Active Comparator
Arm Title
temsirolimus (Torisel) 75mg weekly
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Other Intervention Name(s)
Torisel
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Other Intervention Name(s)
Torisel
Intervention Description
75mg IV once a week until until disease progression, provided that patient is tolerating treatment and getting clinical benefit
Primary Outcome Measure Information:
Title
Independently Assessed Progression-free Survival (PFS)
Description
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.
Time Frame
From randomization date to the date of first documentation of progression or death (average follow up done for 15 months)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS is defined as the time from the date of randomization to the date of death due to any cause.
Time Frame
From randomization date until death due to any cause (average follow up done for 56.1 months)
Title
Independent Assessment - Objective Response Rate (ORR = CR + PR)
Description
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.
Time Frame
From randomization date until end of treatment (average follow up done for 15 months)
Title
Investigator's Assessment ORR (ORR = CR + PR)
Description
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.
Time Frame
From randomization date until end of treatment (average follow up done for 15 months)
Title
Investigator Assessed PFS
Description
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.
Time Frame
From randomization date to the date of first documentation of progression or death (average follow up done for 15 months)
Title
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)
Description
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.
Time Frame
From screening up to a maximum of 57.1 months
Title
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)
Description
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.
Time Frame
From screening up to a maximum of 57.1 months
Title
Quantify the Potential Effect of TEMSR on AUC and Cmax
Description
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
Time Frame
From one week predose (Day -7, -4hr, -8hr, -48hr) upto 2 weeks post dose (4hr, 8hr, 48hr and Day 8)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Mercy Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Veterans Affairs New Jersey Healthcare System-Hematology/Oncology Section (111)
City
East Orange
State/Province
New Jersey
ZIP/Postal Code
07018
Country
United States
Facility Name
Mercy Clinic Oklahoma Communities dba Mercy Clinic Oncology/Hematology-McAuley
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
Mercy Hospital Oklahoma City-Oncology Infusion
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
Amy Shen, RPh
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States
Facility Name
VA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Box Hill Hospital
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Fakultni nemocnice Kralovske Vinohrady
City
Praha 10
State/Province
Czech Republic
ZIP/Postal Code
10034
Country
Czechia
Facility Name
Fakultni nemocnice Kralovske Vinohrady
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
CHU de Nancy
City
Vandoeuvre les Nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Klinik fuer Onkologie und Haematologie, Medizinische Klinik IV
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Presidio Ferrarotto - A.O.U. - PoliclinicoVittorio Emanuele
City
Catania
ZIP/Postal Code
95124
Country
Italy
Facility Name
Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
City
Modena
ZIP/Postal Code
41124
Country
Italy
Facility Name
Struttura Complessa di Ematologia, Dipartimento di Oncologia ed Ematologia-
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Severance Hospital, Yonsei University
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Malopolskie Centrum Medyczne S.C.
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Institutul Clinic Fundeni Bucuresti, Sectia II Hematologie
City
Bucuresti
ZIP/Postal Code
022328
Country
Romania
Facility Name
Spitalul Clinic Coltea, Clinica de Hematologie
City
Bucuresti
ZIP/Postal Code
030171
Country
Romania
Facility Name
Spitalul Universitar de Urgenta Bucuresti, Clinica de Hematologie
City
Bucuresti
ZIP/Postal Code
050098
Country
Romania
Facility Name
Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republic
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
GBOU VPO "First Saint-Petersburg State Medical University n.a. I.P.Pavlov"
City
Saint-Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva
City
Saint-Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Clinical Centre of Serbia,Clinic for Hematology
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Oncology Institute of Vojvodina
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3066K1-4438&StudyName=Comparison%20Of%202%20Doses%20Of%20Temsirolimus%20%28Torisel%29%20In%20Patients%20With%20Mantle%20Cell%20Lymphoma
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
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