Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
- Registration Number
- NCT01180049
- Lead Sponsor
- Pfizer
- Brief Summary
This study will compare the effectiveness and safety of two different doses of temsirolimus (Torisel).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description temsirolimus (Torisel) 175mg weekly x 3, then 75mg weekly temsirolimus - temsirolimus (Torisel) 75mg weekly temsirolimus -
- Primary Outcome Measures
Name Time Method Independently Assessed Progression-free Survival (PFS) From randomization date to the date of first documentation of progression or death (average follow up done for 15 months) 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
Name Time Method Overall Survival (OS) From randomization date until death due to any cause (average follow up done for 56.1 months) 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) From randomization date until end of treatment (average follow up done for 15 months) 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) From randomization date until end of treatment (average follow up done for 15 months) 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 From randomization date to the date of first documentation of progression or death (average follow up done for 15 months) 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) From screening up to a maximum of 57.1 months 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) From screening up to a maximum of 57.1 months 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 From one week predose (Day -7, -4hr, -8hr, -48hr) upto 2 weeks post dose (4hr, 8hr, 48hr and Day 8) 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
Trial Locations
- Locations (30)
Spitalul Universitar de Urgenta Bucuresti, Clinica de Hematologie
🇷🇴Bucuresti, Romania
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Mercy Research Institute
🇺🇸Miami, Florida, United States
VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
Mercy Hospital Oklahoma City-Oncology Infusion
🇺🇸Oklahoma City, Oklahoma, United States
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik
🇩🇪Mainz, Germany
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Mercy Clinic Oklahoma Communities dba Mercy Clinic Oncology/Hematology-McAuley
🇺🇸Oklahoma City, Oklahoma, United States
Amy Shen, RPh
🇺🇸Seattle, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Veterans Affairs New Jersey Healthcare System-Hematology/Oncology Section (111)
🇺🇸East Orange, New Jersey, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Oncology Institute of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
Klinik fuer Onkologie und Haematologie, Medizinische Klinik IV
🇩🇪Aachen, Germany
Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
🇮🇹Modena, Italy
Clinical Centre of Serbia,Clinic for Hematology
🇷🇸Belgrade, Serbia
Struttura Complessa di Ematologia, Dipartimento di Oncologia ed Ematologia-
🇮🇹Torino, Italy
Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Russian Federation
Spitalul Clinic Coltea, Clinica de Hematologie
🇷🇴Bucuresti, Romania
Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva
🇷🇺Saint-Petersburg, Russian Federation
Institutul Clinic Fundeni Bucuresti, Sectia II Hematologie
🇷🇴Bucuresti, Romania
Malopolskie Centrum Medyczne S.C.
🇵🇱Krakow, Poland
CHU de Nancy
🇫🇷Vandoeuvre les Nancy, France
Presidio Ferrarotto - A.O.U. - PoliclinicoVittorio Emanuele
🇮🇹Catania, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
GBOU VPO "First Saint-Petersburg State Medical University n.a. I.P.Pavlov"
🇷🇺Saint-Petersburg, Russian Federation