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Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome

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ClinicalTrials.gov Identifier: NCT00369629
Recruitment Status : Terminated (This was planned as a phase I/II study originally, but due to a lack of funding, the phase II portion was never conducted.)
First Posted : August 29, 2006
Results First Posted : October 9, 2018
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Eli Lilly and Company
Information provided by (Responsible Party):
Northwestern University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma
Interventions Drug: Gemcitabine
Drug: Pemetrexed
Enrollment 14
Recruitment Details The study opened for accrual on June 6, 2006 in phase I with a 3+3 cohort design to find the recommended phase II dose. Phase II would expand to enroll a total of 20 evaluable patients at the recommended dose. The study was closed permanently on September 12, 2012 after 14 patients had been enrolled in the phase I part.
Pre-assignment Details  
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 400 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1000 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1200 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Period Title: Treated 2 Cycles/Reached First Response
Started 6 3 5 0 [1]
Completed 4 2 3 0
Not Completed 2 1 2 0
Reason Not Completed
Physician Decision             0             1             1             0
Adverse Event             0             0             1             0
Progressive disease             2             0             0             0
[1]
No patients were enrolled at this dose level as the study closed early due to lack of funding.
Period Title: Moved on to 4 More Cycles
Started 4 2 3 0
Completed 4 2 2 0
Not Completed 0 0 1 0
Reason Not Completed
Progressive Disease             0             0             1             0
Period Title: Completed 4 More Cycles
Started 4 2 2 0
Completed 0 0 0 0
Not Completed 4 2 2 0
Reason Not Completed
Withdrawal by Subject             2             1             0             0
Progressive disease             2             1             2             0
Period Title: Follow up for 1 Year
Started 6 [1] 3 5 0
Completed 4 1 2 0
Not Completed 2 2 3 0
Reason Not Completed
Death             2             1             1             0
Lost to Follow-up             0             1             0             0
stopped being followed as study closed             0             0             2             0
[1]
All patients treated on study go into the follow up period
Arm/Group Title Gemcitabine and Pemetrexed Disodium
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Gemcitabine: Patients will be treated in cohorts of 3-6 per cohort. The starting dose of gemcitabine will be 800 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle. The dose will be escalated for each subsequent cohort of patients, up to a maximum of 1200 mg/m^2.

Pemetrexed: Patients will be treated in cohorts of 3-6 per cohort. The starting dose of pemetrexed will be 400 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle. The dose will be escalated for each subsequent cohort of patients, up to a maximum of 500 mg/m^2.

Overall Number of Baseline Participants 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
<=18 years
0
   0.0%
Between 18 and 65 years
10
  71.4%
>=65 years
4
  28.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Female
5
  35.7%
Male
9
  64.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Hispanic or Latino
1
   7.1%
Not Hispanic or Latino
13
  92.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
  21.4%
White
11
  78.6%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 14 participants
14
 100.0%
1.Primary Outcome
Title Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort.
Hide Description

Only dose limiting toxicities (DLT) were collected. DLTs were graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

The occurrence of any of the following toxicities during the first treatment cycle constitutes DLT in this study:

Grade 3 and/or 4 non-hematologic toxicity other than grade 3 nausea or vomiting.

Grade 3 and/or 4 unexpected non-hematologic toxicities. Grade 4 vomiting despite maximal antiemetic support. Grade 4 neutropenia and fever during first cycle. Grade 4 neutropenia on Day 1 of 2nd treatment cycle despite growth factor support or grade 4 thrombocytopenia on Day 1 of 2nd treatment cycle.

Time Frame From the day that the first treatment is given through the first 28 day period for each patient.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that experienced a DLT in the first cycle in each cohort. If one DLT is seen in the first 3 patients then 3 more patients are enrolled in that cohort. MTD and is defined as the lowest dose level at which two or more patients experience a DLT. The study closed before enough patients were enrolled to determine the MTD or define DLTs.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 400 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1000 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1200 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Overall Number of Participants Analyzed 6 3 5 0
Measure Type: Number
Unit of Measure: DLT
Perforated sigmoid diverticulitis 1 0 0
Febrile neutropenia 0 0 1
Time Frame Adverse events were collected over a 6 year period for the study. Adverse events were collected from the start of treatment every 14 days until 30 days after the last treatment, for a maximum of 6 cycles. 1 cycle =28 days.
Adverse Event Reporting Description Adverse events were collected every 14 days on a 28 day cycle from the start of treatment until 30 days after the last dose for a maximum of 6 cycles of treatment.
 
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 400 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1000 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

Patients will be treated in cohorts of 3-6 per cohort in a dose escalation of pemetrexed and gemcitabine

Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle.

Gemcitabine at a dose of 1200 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle.

All-Cause Mortality
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)      2/3 (66.67%)      2/5 (40.00%)      0/0    
Hide Serious Adverse Events
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/5 (40.00%)      0/3 (0.00%)      1/5 (20.00%)      0/0    
Gastrointestinal disorders         
Perforated sigmoid diverticulitis  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/0  0
Infections and infestations         
Bacteremia CMV  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/0  0
Febrile neutropenia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/0  0
Pneumonia  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/0  0
Line sepsis and neutropenia  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/0  0
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      3/3 (100.00%)      5/5 (100.00%)      0/0    
Blood and lymphatic system disorders         
Hemoglobin  1  6/6 (100.00%)  2/3 (66.67%)  4/5 (80.00%)  0/0 
Neutrophils (neutropenia)  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Leukocytes (total white blood cells)  1  3/6 (50.00%)  1/3 (33.33%)  2/5 (40.00%)  0/0 
Lymphopenia  1  5/6 (83.33%)  1/3 (33.33%)  4/5 (80.00%)  0/0 
Platelets (thrombocytopenia)  1  4/6 (66.67%)  1/3 (33.33%)  2/5 (40.00%)  0/0 
Edema, Limb  1  1/6 (16.67%)  0/3 (0.00%)  4/5 (80.00%)  0/0 
Edema  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Edema, trunk/genital  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Cardiac disorders         
Hypotension  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Tachycardia  1  1/6 (16.67%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Ear and labyrinth disorders         
Otitis, external ear  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Eye disorders         
Blurred vision  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Watery eye (epiphora, tearing)  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Gastrointestinal disorders         
Anorexia  1  0/6 (0.00%)  1/3 (33.33%)  1/5 (20.00%)  0/0 
Constipation  1  0/6 (0.00%)  1/3 (33.33%)  4/5 (80.00%)  0/0 
Dehydration  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Diarrhea  1  0/6 (0.00%)  1/3 (33.33%)  3/5 (60.00%)  0/0 
Heartburn/dyspepsia  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Nausea  1  2/6 (33.33%)  1/3 (33.33%)  2/5 (40.00%)  0/0 
Stomach pain  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Taste alteration (dysgeusia)  1  1/6 (16.67%)  1/3 (33.33%)  1/5 (20.00%)  0/0 
Vomiting  1  1/6 (16.67%)  0/3 (0.00%)  3/5 (60.00%)  0/0 
Abdomen pain  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
General disorders         
Fatigue  1  2/6 (33.33%)  3/3 (100.00%)  4/5 (80.00%)  0/0 
Fever  1  1/6 (16.67%)  0/3 (0.00%)  3/5 (60.00%)  0/0 
Insomnia  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Rigor/chills  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Sweating/diaphoresis  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Weight loss  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Pain NOS  1  0/6 (0.00%)  1/3 (33.33%)  1/5 (20.00%)  0/0 
Immune system disorders         
allergic rhinitis  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Infections and infestations         
Infection  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Dermatitis  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Colitis, infectious  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Urinary tract infection  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Investigations         
International normalized Ration of prothrombin time (INR)  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Metabolism and nutrition disorders         
Alkaline phosphatase  1  4/6 (66.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
ALT increase  1  0/6 (0.00%)  2/3 (66.67%)  1/5 (20.00%)  0/0 
AST increase  1  4/6 (66.67%)  2/3 (66.67%)  3/5 (60.00%)  0/0 
Albumin, serum-low  1  4/6 (66.67%)  1/3 (33.33%)  5/5 (100.00%)  0/0 
Bilirubin (hyperbilirubinemia)  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Creatinine  1  5/6 (83.33%)  1/3 (33.33%)  2/5 (40.00%)  0/0 
Calcium, serum-high (hypercalcemia)  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Calcium, serum-low (hypocalcemia)  1  2/6 (33.33%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Glucose, serum-high (hyperglycemia)  1  4/6 (66.67%)  3/3 (100.00%)  4/5 (80.00%)  0/0 
Glucose, Serum-low (hypoglycemia)  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Potassium, serum-low (hypokalemia)  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Sodium, serum-high (hypernatremia)  1  2/6 (33.33%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Sodium, serum low (hyponatremia)  1  1/6 (16.67%)  0/3 (0.00%)  2/5 (40.00%)  0/0 
Musculoskeletal and connective tissue disorders         
Limb pain  1  0/6 (0.00%)  0/3 (0.00%)  2/5 (40.00%)  0/0 
Nervous system disorders         
Sensory Neuropathy  1  0/6 (0.00%)  0/3 (0.00%)  2/5 (40.00%)  0/0 
Mental status  1  1/6 (16.67%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Anxiety (mood alteration)  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Depression (mood alteration)  1  0/6 (0.00%)  1/3 (33.33%)  0/5 (0.00%)  0/0 
Headache  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Renal and urinary disorders         
Hemorrhage, GU: Urinary NOS  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Renal failure  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Reproductive system and breast disorders         
Scrotum pain  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Urethra pain  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Shortness of breath (dyspnea)  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
Tachypnea  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Skin and subcutaneous tissue disorders         
Flushing  1  0/6 (0.00%)  0/3 (0.00%)  2/5 (40.00%)  0/0 
Hair loss (alopecia)  1  0/6 (0.00%)  0/3 (0.00%)  2/5 (40.00%)  0/0 
Pruritus/itching  1  4/6 (66.67%)  1/3 (33.33%)  1/5 (20.00%)  0/0 
Cellulitis  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
MRSA  1  0/6 (0.00%)  0/3 (0.00%)  1/5 (20.00%)  0/0 
Vascular disorders         
Thrombosis  1  1/6 (16.67%)  0/3 (0.00%)  0/5 (0.00%)  0/0 
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
The study was terminated early before the last patient was enrolled in phase I due to lack of funding. The phase II portion was never conducted.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Barbara Pro
Organization: Northwestern University
EMail: barbara.pro@nm.org
Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00369629    
Other Study ID Numbers: NU 05H8
P30CA060553 ( U.S. NIH Grant/Contract )
STU00006771 ( Other Identifier: Northwestern University IRB )
First Submitted: August 24, 2006
First Posted: August 29, 2006
Results First Submitted: August 1, 2018
Results First Posted: October 9, 2018
Last Update Posted: August 28, 2019