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Study Evaluating Temsirolimus (CCI-779) In Mantle Cell Lymphoma (MCL) (OPTIMAL)

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: NCT00117598
Recruitment Status : Completed
First Posted : July 7, 2005
Results First Posted : March 6, 2012
Last Update Posted : March 30, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma
Interventions Drug: Temsirolimus (CCI-779)
Drug: Investigator's choice
Enrollment 169
Recruitment Details  
Pre-assignment Details September 5, 2007: Sponsor conducted primary analysis of progression free survival. As a result of these preliminary data, participants receiving investigator choice therapy and those receiving 175/25 mg temsirolimus could cross over to receive treatment with 175/75 mg temsirolimus (Protocol Amendment 5).
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Temsirolimus 175/25 mg Then 75 mg Investigator's Choice Then Temsirolimus 175/75 mg
Hide Arm/Group Description Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Temsirolimus 175 mg administered IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until treatment cross over allowed (via Protocol Amendment 5), then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Participants received 1 single-agent treatment chosen by investigator until treatment cross over allowed (via Protocol Amendment 5), then temsirolimus 175 mg IV once weekly for 3 weeks; then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Period Title: Prior to Treatment Cross Over
Started 57 56 56 0 0
Completed 0 3 4 0 0
Not Completed 57 53 52 0 0
Reason Not Completed
Death             40             41             37             0             0
Lost to Follow-up             0             2             2             0             0
Withdrawal by Subject             2             1             4             0             0
Other             15             9             9             0             0
Period Title: After Treament Cross Over
Started 0 0 0 3 4
Completed 0 0 0 0 0
Not Completed 0 0 0 3 4
Reason Not Completed
Death             0             0             0             1             2
Withdrawal by Subject             0             0             0             1             0
Other             0             0             0             1             2
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Total
Hide Arm/Group Description Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Total of all reporting groups
Overall Number of Baseline Participants 57 56 56 169
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Years
Number Analyzed 57 participants 56 participants 56 participants 169 participants
<65 years 24 17 28 69
>=65 years 33 39 28 100
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 56 participants 56 participants 169 participants
Female
9
  15.8%
15
  26.8%
8
  14.3%
32
  18.9%
Male
48
  84.2%
41
  73.2%
48
  85.7%
137
  81.1%
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description The period from randomization until disease progression, death or date of last contact.
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: All randomized participants at time of primary analysis
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 54 54 54
Median (95% Confidence Interval)
Unit of Measure: months
4.8
(2.9 to 7.0)
3.7
(3.4 to 6.2)
1.8
(1.6 to 2.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments Two null hypotheses (Ho) tested: 1. PFS distributions for temsirolimus 175/75 mg and investigator’s choice treatment groups are identical. 2. PFS distributions for temsirolimus 175/25 mg and investigator's choice treatment groups are identical. Alternative hypothesis (Ha) for each test was that PFS distributions differed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.25 to 0.63
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.26 to 0.65
Estimation Comments HR from a cox model adjusted for baseline stratification factors
2.Secondary Outcome
Title Percentage of Participants With Objective Response
Hide Description Assessment of complete or partial response (CR, PR) or uncomplete response (CRu) using Response Evaluation Criteria in Solid Tumors. CR: 1) No disease evident. 2) Lymph node, nodal mass regressed to normal size. 3) Previously enlarged organ ↓ size. 4) Bone marrow clear on repeat aspirate, biopsy. CRu: CR 1 and 3, at least 1 of following: Lymph node regressed >75%. Bone marrow ↑ number or aggregate size, no cytologic/architectural atypia. PR: ≥50% ↓ index lesion, no size ↑ in other nodes, liver, spleen. Splenic and hepatic nodule regressed ≥50%. No new disease.
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 54 54 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.2
(11.1 to 33.3)
5.6
(0.0 to 11.7)
1.9
(0.0 to 5.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6179
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Other Pre-specified Outcome
Title Overall Survival (OS)
Hide Description Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.
Time Frame Baseline up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 54 54 54
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(8.2 to 18.0)
8.8
(6.4 to 14.5)
9.5
(5.3 to 15.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3053
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.46 to 1.28
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9515
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.60 to 1.62
Estimation Comments HR from a cox model adjusted for baseline stratification factors
4.Other Pre-specified Outcome
Title Time to Response
Hide Description Time between the date of randomization and the first date of objective response for participants with a confirmed objective response.
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT subset of participants with a confirmed objective response
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 12 3 1
Median (95% Confidence Interval)
Unit of Measure: months
3.6
(3.5 to 4.0)
3.5
(3.5 to 4.1)
4.0 [1] 
(NA to NA)
[1]
Not Available (NA), only 1 participant with a response
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.14 to 9.01
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.10 to 13.3
Estimation Comments HR from a cox model adjusted for baseline stratification factors
5.Other Pre-specified Outcome
Title Duration of Response
Hide Description Time from the first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented; censored at last valid tumor assessment.
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT subset of participants who had a response
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 12 3 1
Median (95% Confidence Interval)
Unit of Measure: months
7.1 [1] 
(4.1 to NA)
3.6
(3.2 to 10.6)
NA [2] 
(NA to NA)
[1]
unable to calculate, data too limited for accurate assessment
[2]
NA, unable to calculate, only 1 participant with a response
6.Other Pre-specified Outcome
Title Time to Failure (TTF)
Hide Description TTF is defined as the time from randomization to the date of the first documentation of Progressive Disease (PD), the date of treatment discontinuation except completion of treatment, or date of death (any cause).
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 54 54 54
Median (95% Confidence Interval)
Unit of Measure: months
3.1
(2.4 to 5.5)
3.4
(2.7 to 5.1)
1.7
(1.4 to 1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.23 to 0.56
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.26 to 0.60
Estimation Comments HR from a cox model adjusted for baseline stratification factors
7.Other Pre-specified Outcome
Title Time to Tumor Progression (TTP)
Hide Description TTP: time from randomization to first documentation of objective tumor progression (including recurrence); censored at last valid tumor assessment.
Time Frame Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice
Hide Arm/Group Description:
Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Overall Number of Participants Analyzed 54 54 54
Median (95% Confidence Interval)
Unit of Measure: months
5.2
(4.2 to 9.1)
3.5
(1.9 to 6.2)
1.9
(1.6 to 2.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/75 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.23 to 0.67
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Temsirolimus 175/25 mg, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0712
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.40 to 1.04
Estimation Comments HR from a cox model adjusted for baseline stratification factors
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Temsirolimus 175/25 mg Then 75 mg Investigator's Choice Then Temsirolimus 175/75 mg
Hide Arm/Group Description Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Includes participants who received Temsirolimus 175/75 mg prior to crossover (Protocol Amendment 5). Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment, chosen by investigator:

  1. Fludarabine 25 milligram per meter squared (mg/m^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
  2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
  3. Gemcitabine 1 g/m^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
  4. Cyclophosphamide 300 (200-450) mg/m^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m^2 IV every 21 to 28 days;
  5. Cladribine 5 mg/m^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
  6. Etoposide 50 (50-150) mg/m^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m^2 PO daily for 3-5 days every 21 to 28 days;
  7. Prednisone 40 (20-60) mg/m^2 PO daily or every other day;
  8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.
Temsirolimus 175 mg administered IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until treatment cross over allowed (via Protocol Amendment 5), then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Adverse events (AEs) presented for these participants after they crossed over to 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Participants received 1 single-agent treatment chosen by investigator until treatment cross over allowed (via Protocol Amendment 5), then temsirolimus 175 mg IV once weekly for 3 weeks; then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. AEs presented for these participants after they crossed over to 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.
All-Cause Mortality
Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Temsirolimus 175/25 mg Then 75 mg Investigator's Choice Then Temsirolimus 175/75 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Temsirolimus 175/25 mg Then 75 mg Investigator's Choice Then Temsirolimus 175/75 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/57 (59.65%)   34/56 (60.71%)   14/54 (25.93%)   1/3 (33.33%)   1/4 (25.00%) 
Blood and lymphatic system disorders           
Acute Lymphoblastic Leukemia * 1 [1]  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Leukocytosis * 1  2/57 (3.51%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Leukopenia * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Lymphoma * 1  1/57 (1.75%)  2/56 (3.57%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Neutropenia * 1  1/57 (1.75%)  0/56 (0.00%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Thrombocytopenia * 1  0/57 (0.00%)  4/56 (7.14%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Cardiac disorders           
Angina Pectoris * 1 [2]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Atrial Flutter * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Cerebrovascular Accident * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Endocarditis * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Heart Failure * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Hypervolemia * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Pulmonary Embolus * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Syncope * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Tachycardia * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Ventricular Tachycardia * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Eye disorders           
Conjunctivitis * 1 [3]  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders           
Anorexia * 1 [4]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Diarrhea * 1  4/57 (7.02%)  4/56 (7.14%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Duodenal Ulcer Perforation * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Enteritis * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Gastritis * 1  1/57 (1.75%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Gastroenteritis * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Gastrointestinal Hemorrhage * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Liver Function Tests Abnormal * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Melena * 1  1/57 (1.75%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Mouth Ulceration * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Rectal Disorder * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Rectal Hemorrhage * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Stomatitis * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Ulcerative Colitis * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
General disorders           
Abdominal Pain * 1 [5]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Accidental Injury * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Asthenia * 1  2/57 (3.51%)  3/56 (5.36%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Back Pain * 1  0/57 (0.00%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Cellulitis * 1  2/57 (3.51%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Chills * 1  1/57 (1.75%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Fever * 1  8/57 (14.04%)  7/56 (12.50%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
General Physical Health Deterioration * 1  3/57 (5.26%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Headache * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Infection * 1  3/57 (5.26%)  2/56 (3.57%)  2/54 (3.70%)  0/3 (0.00%)  1/4 (25.00%) 
Neutropenic Fever * 1  3/57 (5.26%)  1/56 (1.79%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Sepsis * 1  2/57 (3.51%)  1/56 (1.79%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Septic Shock * 1  1/57 (1.75%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders           
Creatinine Increased * 1 [6]  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Dehydration * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Edema * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Hypoglycemia * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypokalemia * 1  2/57 (3.51%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Peripheral Edema * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Nervous system disorders           
Facial Paralysis * 1 [7]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Neuralgia * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Somnolence * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders           
Acute Kidney Failure * 1 [8]  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Genital Edema * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Kidney Function Abnormal * 1  0/57 (0.00%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Urinary Retention * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Bronchitis * 1 [9]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Carcinoma Of Lung * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Cough Increased * 1  1/57 (1.75%)  2/56 (3.57%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Dyspnea * 1  0/57 (0.00%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Eosinophilic Pneumonia * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Epistaxis * 1  2/57 (3.51%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hyperventilation * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypoxia * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Interstitial Pneumonia * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lung Disorder * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lung Edema * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lung Fibrosis * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lung Infiltration Nos * 1  1/57 (1.75%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pleural Effusion * 1  0/57 (0.00%)  1/56 (1.79%)  1/54 (1.85%)  1/3 (33.33%)  0/4 (0.00%) 
Pleuritic Pain * 1  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Pneumonia * 1  6/57 (10.53%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  1/4 (25.00%) 
Pneumonitis * 1  1/57 (1.75%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory Distress Syndrome * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory Failure * 1  1/57 (1.75%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Rhinitis * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne * 1 [10]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Fungal Dermatitis * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Herpes Zoster * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Rash * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Skin Carcinoma * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, COSTART, 5th edition
[1]
Hemic And Lymphatic System
[2]
Cardiovascular System
[3]
Special Senses
[4]
Digestive System
[5]
Body as a whole
[6]
Metabolic And Nutritional
[7]
Nervous System
[8]
Urogenital System
[9]
Respiratory System
[10]
Skin And Appendages
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Temsirolimus 175/75 mg Temsirolimus 175/25 mg Investigator's Choice Temsirolimus 175/25 mg Then 75 mg Investigator's Choice Then Temsirolimus 175/75 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/57 (100.00%)   56/56 (100.00%)   52/54 (96.30%)   3/3 (100.00%)   4/4 (100.00%) 
Blood and lymphatic system disorders           
Anemia * 1 [1]  31/57 (54.39%)  30/56 (53.57%)  24/54 (44.44%)  1/3 (33.33%)  3/4 (75.00%) 
Ecchymosis * 1  4/57 (7.02%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Leukocytosis * 1  3/57 (5.26%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Leukopenia * 1  10/57 (17.54%)  12/56 (21.43%)  22/54 (40.74%)  1/3 (33.33%)  1/4 (25.00%) 
Lymphadenopathy * 1  3/57 (5.26%)  2/56 (3.57%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Lymphedema * 1  3/57 (5.26%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lymphocytosis * 1  3/57 (5.26%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lymphopenia * 1  7/57 (12.28%)  7/56 (12.50%)  10/54 (18.52%)  0/3 (0.00%)  0/4 (0.00%) 
Neutropenia * 1  15/57 (26.32%)  19/56 (33.93%)  22/54 (40.74%)  2/3 (66.67%)  1/4 (25.00%) 
Prothrombin Time Prolonged * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Thrombocytopenia * 1  45/57 (78.95%)  47/56 (83.93%)  29/54 (53.70%)  3/3 (100.00%)  4/4 (100.00%) 
Cardiac disorders           
Hemorrhage * 1 [2]  3/57 (5.26%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Hypertension * 1  2/57 (3.51%)  5/56 (8.93%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypotension * 1  2/57 (3.51%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Tachycardia * 1  5/57 (8.77%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Tachycardia Sinus * 1  1/57 (1.75%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Thrombophlebitis * 1  0/57 (0.00%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Eye disorders           
Abnormal Vision * 1 [3]  3/57 (5.26%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Conjunctivitis * 1  4/57 (7.02%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Diplopia * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Eye Disorder * 1  3/57 (5.26%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Eye Hemorrhage * 1  3/57 (5.26%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Parosmia * 1  3/57 (5.26%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Taste Loss * 1  5/57 (8.77%)  3/56 (5.36%)  0/54 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Taste Perversion * 1  9/57 (15.79%)  2/56 (3.57%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders           
Abdominal Distension * 1 [4]  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Anorexia * 1  23/57 (40.35%)  17/56 (30.36%)  8/54 (14.81%)  1/3 (33.33%)  0/4 (0.00%) 
Aphthous Stomatitis * 1  3/57 (5.26%)  4/56 (7.14%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Blood In Stool * 1  1/57 (1.75%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Constipation * 1  9/57 (15.79%)  4/56 (7.14%)  10/54 (18.52%)  0/3 (0.00%)  2/4 (50.00%) 
Diarrhea * 1  26/57 (45.61%)  19/56 (33.93%)  6/54 (11.11%)  1/3 (33.33%)  0/4 (0.00%) 
Dry Mouth * 1  4/57 (7.02%)  2/56 (3.57%)  1/54 (1.85%)  0/3 (0.00%)  1/4 (25.00%) 
Dyspspsia * 1  2/57 (3.51%)  2/56 (3.57%)  3/54 (5.56%)  0/3 (0.00%)  0/4 (0.00%) 
Dysphagia * 1  6/57 (10.53%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Melena * 1  3/57 (5.26%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Mouth Pain * 1  1/57 (1.75%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Mouth Ulceration * 1  3/57 (5.26%)  5/56 (8.93%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Mucositis * 1  21/57 (36.84%)  9/56 (16.07%)  0/54 (0.00%)  1/3 (33.33%)  2/4 (50.00%) 
Nausea * 1  14/57 (24.56%)  17/56 (30.36%)  11/54 (20.37%)  1/3 (33.33%)  2/4 (50.00%) 
Rectal Hemorrhage * 1  5/57 (8.77%)  1/56 (1.79%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Stomatitis * 1  12/57 (21.05%)  6/56 (10.71%)  3/54 (5.56%)  0/3 (0.00%)  0/4 (0.00%) 
Vomiting * 1  8/57 (14.04%)  7/56 (12.50%)  3/54 (5.56%)  0/3 (0.00%)  2/4 (50.00%) 
General disorders           
Abdominal Pain * 1 [5]  14/57 (24.56%)  16/56 (28.57%)  9/54 (16.67%)  0/3 (0.00%)  2/4 (50.00%) 
Accidental Injury * 1  4/57 (7.02%)  6/56 (10.71%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Asthenia * 1  38/57 (66.67%)  34/56 (60.71%)  13/54 (24.07%)  3/3 (100.00%)  1/4 (25.00%) 
Back Pain * 1  8/57 (14.04%)  8/56 (14.29%)  2/54 (3.70%)  0/3 (0.00%)  1/4 (25.00%) 
Cellulitis * 1  1/57 (1.75%)  2/56 (3.57%)  2/54 (3.70%)  0/3 (0.00%)  1/4 (25.00%) 
Chest Pain * 1  6/57 (10.53%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Chills * 1  14/57 (24.56%)  5/56 (8.93%)  6/54 (11.11%)  0/3 (0.00%)  0/4 (0.00%) 
Face Edema * 1  4/57 (7.02%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Fever * 1  21/57 (36.84%)  16/56 (28.57%)  17/54 (31.48%)  0/3 (0.00%)  2/4 (50.00%) 
Flu Syndrome * 1  2/57 (3.51%)  5/56 (8.93%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Headache * 1  9/57 (15.79%)  13/56 (23.21%)  5/54 (9.26%)  0/3 (0.00%)  2/4 (50.00%) 
Hernia * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Infection * 1  17/57 (29.82%)  15/56 (26.79%)  3/54 (5.56%)  0/3 (0.00%)  2/4 (50.00%) 
Neoplasm * 1  2/57 (3.51%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Non-Specified Drug Reaction * 1  3/57 (5.26%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pain * 1  19/57 (33.33%)  13/56 (23.21%)  2/54 (3.70%)  1/3 (33.33%)  2/4 (50.00%) 
Pelvic Pain * 1  0/57 (0.00%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Investigations           
Local Reaction To Procedure * 1 [6]  3/57 (5.26%)  3/56 (5.36%)  1/54 (1.85%)  1/3 (33.33%)  0/4 (0.00%) 
Metabolism and nutrition disorders           
Creatinine Increased * 1 [7]  5/57 (8.77%)  7/56 (12.50%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Dehydration * 1  2/57 (3.51%)  4/56 (7.14%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Edema * 1  3/57 (5.26%)  6/56 (10.71%)  6/54 (11.11%)  0/3 (0.00%)  0/4 (0.00%) 
Gamma Globulin Decreased * 1  3/57 (5.26%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypercholesteremia * 1  11/57 (19.30%)  10/56 (17.86%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hyperglycemia * 1  9/57 (15.79%)  6/56 (10.71%)  6/54 (11.11%)  0/3 (0.00%)  1/4 (25.00%) 
Hyperlipemia * 1  7/57 (12.28%)  11/56 (19.64%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Hypocalcemia * 1  6/57 (10.53%)  5/56 (8.93%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypokalemia * 1  14/57 (24.56%)  10/56 (17.86%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Hyponatremia * 1  2/57 (3.51%)  0/56 (0.00%)  1/54 (1.85%)  0/3 (0.00%)  1/4 (25.00%) 
Hypophosphatemia * 1  7/57 (12.28%)  6/56 (10.71%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Hypoproteinemia * 1  2/57 (3.51%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Lactic Dehydrogenase Increased * 1  6/57 (10.53%)  5/56 (8.93%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Peripheral Edema * 1  14/57 (24.56%)  13/56 (23.21%)  9/54 (16.67%)  0/3 (0.00%)  1/4 (25.00%) 
SGOT Increased * 1  2/57 (3.51%)  6/56 (10.71%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
SGPT Increased * 1  1/57 (1.75%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Weight Gain * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Weight Loss * 1  10/57 (17.54%)  12/56 (21.43%)  5/54 (9.26%)  0/3 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1 [8]  12/57 (21.05%)  5/56 (8.93%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Bone Pain * 1  1/57 (1.75%)  3/56 (5.36%)  0/54 (0.00%)  1/3 (33.33%)  1/4 (25.00%) 
Joint Disorder * 1  4/57 (7.02%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Leg Cramps * 1  3/57 (5.26%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Muscle Cramp * 1  7/57 (12.28%)  2/56 (3.57%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Myalgia * 1  5/57 (8.77%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Nervous system disorders           
Anxiety * 1 [9]  9/57 (15.79%)  4/56 (7.14%)  3/54 (5.56%)  0/3 (0.00%)  0/4 (0.00%) 
Depression * 1  5/57 (8.77%)  5/56 (8.93%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Dizziness * 1  4/57 (7.02%)  6/56 (10.71%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Insomnia * 1  12/57 (21.05%)  6/56 (10.71%)  4/54 (7.41%)  0/3 (0.00%)  0/4 (0.00%) 
Neuropathy * 1  2/57 (3.51%)  4/56 (7.14%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Paresthesia * 1  4/57 (7.02%)  6/56 (10.71%)  3/54 (5.56%)  1/3 (33.33%)  0/4 (0.00%) 
Sleep Disorder * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Renal and urinary disorders           
Dysuria * 1 [10]  4/57 (7.02%)  5/56 (8.93%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Hematuria * 1  1/57 (1.75%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Urinary Frequency * 1  4/57 (7.02%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Urinary Tract Infection * 1  3/57 (5.26%)  5/56 (8.93%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Bronchitis * 1 [11]  4/57 (7.02%)  3/56 (5.36%)  3/54 (5.56%)  0/3 (0.00%)  0/4 (0.00%) 
Cough Increased * 1  19/57 (33.33%)  18/56 (32.14%)  5/54 (9.26%)  0/3 (0.00%)  0/4 (0.00%) 
Dyspnea * 1  13/57 (22.81%)  12/56 (21.43%)  16/54 (29.63%)  1/3 (33.33%)  2/4 (50.00%) 
Epistaxis * 1  26/57 (45.61%)  16/56 (28.57%)  3/54 (5.56%)  1/3 (33.33%)  2/4 (50.00%) 
Hypoxia * 1  1/57 (1.75%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Pharyngitis * 1  7/57 (12.28%)  9/56 (16.07%)  4/54 (7.41%)  0/3 (0.00%)  0/4 (0.00%) 
Pleural Disorder * 1  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Pleural Effusion * 1  6/57 (10.53%)  3/56 (5.36%)  4/54 (7.41%)  0/3 (0.00%)  0/4 (0.00%) 
Pneumonia * 1  6/57 (10.53%)  8/56 (14.29%)  5/54 (9.26%)  0/3 (0.00%)  1/4 (25.00%) 
Pulmonary Physical Finding * 1  1/57 (1.75%)  5/56 (8.93%)  2/54 (3.70%)  0/3 (0.00%)  0/4 (0.00%) 
Rhinitis * 1  6/57 (10.53%)  5/56 (8.93%)  3/54 (5.56%)  0/3 (0.00%)  0/4 (0.00%) 
Sinusitis * 1  6/57 (10.53%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Upper Respiratory Infection * 1  9/57 (15.79%)  4/56 (7.14%)  2/54 (3.70%)  0/3 (0.00%)  2/4 (50.00%) 
Voice Alteration * 1  3/57 (5.26%)  1/56 (1.79%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne * 1 [12]  5/57 (8.77%)  2/56 (3.57%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Dry Skin * 1  7/57 (12.28%)  5/56 (8.93%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Eczema * 1  3/57 (5.26%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Erythema * 1  6/57 (10.53%)  1/56 (1.79%)  2/54 (3.70%)  1/3 (33.33%)  0/4 (0.00%) 
Fungal Dermatitis * 1  1/57 (1.75%)  3/56 (5.36%)  0/54 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Herpes Simplex * 1  6/57 (10.53%)  10/56 (17.86%)  4/54 (7.41%)  0/3 (0.00%)  1/4 (25.00%) 
Maculopapular Rash * 1  1/57 (1.75%)  3/56 (5.36%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Nail Disorder * 1  11/57 (19.30%)  10/56 (17.86%)  1/54 (1.85%)  0/3 (0.00%)  0/4 (0.00%) 
Night Sweats * 1  5/57 (8.77%)  3/56 (5.36%)  4/54 (7.41%)  0/3 (0.00%)  0/4 (0.00%) 
Pruritic Rash * 1  5/57 (8.77%)  0/56 (0.00%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pruritus * 1  16/57 (28.07%)  12/56 (21.43%)  3/54 (5.56%)  1/3 (33.33%)  1/4 (25.00%) 
Rash * 1  21/57 (36.84%)  19/56 (33.93%)  6/54 (11.11%)  0/3 (0.00%)  0/4 (0.00%) 
Skin Carcinoma * 1  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Skin Disorder * 1  3/57 (5.26%)  3/56 (5.36%)  0/54 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Sweating * 1  1/57 (1.75%)  3/56 (5.36%)  7/54 (12.96%)  0/3 (0.00%)  0/4 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, COSTART, 5th edition
[1]
Hemic And Lymphatic System
[2]
Cardiovascular System
[3]
Special Senses
[4]
Digestive System
[5]
Body As A Whole
[6]
Adverse Event Associated with Miscellaneous factors
[7]
Metabolic And Nutritional
[8]
Musculoskeletal System
[9]
Nervous System
[10]
Urogenital System
[11]
Respiratory System
[12]
Skin And Appendages
After the primary analysis was completed, efficacy data was no longer collected nor analyzed; Participants were followed for safety up to 6 months after the last dose of temsirolimus.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00117598    
Obsolete Identifiers: NCT00326547
Other Study ID Numbers: 3066K1-305
First Submitted: June 30, 2005
First Posted: July 7, 2005
Results First Submitted: February 2, 2012
Results First Posted: March 6, 2012
Last Update Posted: March 30, 2015