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

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01180049
• Other study ID #: 3066K1-4438
• Secondary ID: B17710072009-015
• Status: Completed
• Phase: Phase 4
• Start date: March 2011
• Est. completion date: June 2018

Study information

• Verified date: May 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: June 2018
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

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
• temsirolimus
75mg IV once a week until until disease progression, provided that patient is tolerating treatment and getting clinical benefit

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)

External Links

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