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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01180049
Recruitment Status : Completed
First Posted : August 11, 2010
Results First Posted : May 19, 2017
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE August 9, 2010
First Posted Date  ICMJE August 11, 2010
Results First Submitted Date  ICMJE November 4, 2016
Results First Posted Date  ICMJE May 19, 2017
Last Update Posted Date May 20, 2019
Actual Study Start Date  ICMJE March 2011
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2017)
Independently Assessed Progression-free Survival (PFS) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2010)
  • Estimate independently assessed Progression Free Survival (PFS) [ Time Frame: every 6 weeks for first 2 assessments ]
  • Estimate independently assessed Progression Free Survival (PFS) [ Time Frame: then every 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2019)
  • Overall Survival (OS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2010)
  • Estimate Overall survival [ Time Frame: every 6 months from last dose of study drug ]
  • Estimate objective response rate, independently and investigator assessed [ Time Frame: every 6 weeks for first 2 assessments ]
  • Estimate objective response rate, independently and investigator assessed [ Time Frame: then every 8 weeks ]
  • Estimate investigator assessed PFS [ Time Frame: every 6 weeks for first 2 assessments ]
  • Estimate investigator assessed PFS [ Time Frame: then every 8 weeks ]
  • Assess safety, including adverse events of infection and bleeding [ Time Frame: ongoing ]
  • Quantify potential effect of temsirolimus to alter the disposition of desipramine, a substrate of CYP2D6 metabolism [ Time Frame: first 2 weeks of study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison Of 2 Doses Of Temsirolimus (Torisel) In Patients With Mantle Cell Lymphoma
Official Title  ICMJE A RANDOMIZED PHASE 4 STUDY COMPARING 2 INTRAVENOUS TEMSIROLIMUS (TEMSR) REGIMENS IN SUBJECTS WITH RELAPSED, REFRACTORY MANTLE CELL LYMPHOMA
Brief Summary This study will compare the effectiveness and safety of two different doses of temsirolimus (Torisel).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • 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 Name: Torisel
  • Drug: temsirolimus
    75mg IV once a week until until disease progression, provided that patient is tolerating treatment and getting clinical benefit
    Other Name: Torisel
Study Arms  ICMJE
  • Active Comparator: temsirolimus (Torisel) 175mg weekly x 3, then 75mg weekly
    Intervention: Drug: temsirolimus
  • Active Comparator: temsirolimus (Torisel) 75mg weekly
    Intervention: Drug: temsirolimus
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: April 9, 2018)
101
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2010)
100
Actual Study Completion Date  ICMJE June 2018
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 Australia,   Czechia,   France,   Germany,   Italy,   Korea, Republic of,   Poland,   Romania,   Russian Federation,   Serbia,   United States
Removed Location Countries Belgium,   Bulgaria,   Czech Republic,   Hong Kong,   Hungary,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT01180049
Other Study ID Numbers  ICMJE 3066K1-4438
B1771007 ( Other Identifier: Alias Study Number )
2009-015498-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2019

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