Trial Outcomes & Findings for Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome (NCT NCT00369629)

Last Updated: 2019-08-28

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

From the day that the first treatment is given through the first 28 day period for each patient.

Results posted on

2019-08-28

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Cohort 1 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.	Cohort 2 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.	Cohort 3 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.
Treated 2 Cycles/Reached First Response STARTED	6	3	5
Treated 2 Cycles/Reached First Response COMPLETED	4	2	3
Treated 2 Cycles/Reached First Response NOT COMPLETED	2	1	2
Moved on to 4 More Cycles STARTED	4	2	3
Moved on to 4 More Cycles COMPLETED	4	2	2
Moved on to 4 More Cycles NOT COMPLETED	0	0	1
Completed 4 More Cycles STARTED	4	2	2
Completed 4 More Cycles COMPLETED	0	0	0
Completed 4 More Cycles NOT COMPLETED	4	2	2
Follow up for 1 Year STARTED	6	3	5
Follow up for 1 Year COMPLETED	4	1	2
Follow up for 1 Year NOT COMPLETED	2	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 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.	Cohort 2 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.	Cohort 3 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.
Treated 2 Cycles/Reached First Response Physician Decision	0	1	1
Treated 2 Cycles/Reached First Response Adverse Event	0	0	1
Treated 2 Cycles/Reached First Response Progressive disease	2	0	0
Moved on to 4 More Cycles Progressive Disease	0	0	1
Completed 4 More Cycles Withdrawal by Subject	2	1	0
Completed 4 More Cycles Progressive disease	2	1	2
Follow up for 1 Year Death	2	1	1
Follow up for 1 Year Lost to Follow-up	0	1	0
Follow up for 1 Year stopped being followed as study closed	0	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine and Pemetrexed Disodium n=14 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the day that the first treatment is given through the first 28 day period for each patient.

Population: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=6 Participants 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.	Cohort 2 n=3 Participants 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.	Cohort 3 n=5 Participants 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.	Cohort 4 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.
Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. Perforated sigmoid diverticulitis	1 DLT	0 DLT	0 DLT	—
Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. Febrile neutropenia	0 DLT	0 DLT	1 DLT	—

Adverse Events

Cohort 1

Serious events: 2 serious events

Other events: 6 other events

Deaths: 5 deaths

Cohort 2

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Cohort 3

Serious events: 1 serious events

Other events: 5 other events

Deaths: 2 deaths

Cohort 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=6 participants at risk；n=5 participants at risk 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.	Cohort 2 n=3 participants at risk 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.	Cohort 3 n=5 participants at risk 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.	Cohort 4 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.
Gastrointestinal disorders Perforated sigmoid diverticulitis	20.0% 1/5 • Number of events 1 • 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 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.	0.00% 0/3 • 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 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.	0.00% 0/5 • 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 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.	— 0/0 • 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 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.
Infections and infestations Bacteremia CMV	20.0% 1/5 • Number of events 1 • 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 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.	0.00% 0/3 • 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 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.	0.00% 0/5 • 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 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.	— 0/0 • 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 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.
Infections and infestations Febrile neutropenia	0.00% 0/5 • 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 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.	0.00% 0/3 • 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 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.	20.0% 1/5 • Number of events 1 • 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 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.	— 0/0 • 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 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.
Infections and infestations Pneumonia	20.0% 1/5 • Number of events 1 • 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 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.	0.00% 0/3 • 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 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.	0.00% 0/5 • 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 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.	— 0/0 • 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 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.
Infections and infestations Line sepsis and neutropenia	20.0% 1/5 • Number of events 1 • 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 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.	0.00% 0/3 • 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 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.	0.00% 0/5 • 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 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.	— 0/0 • 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 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.

Other adverse events

Additional Information

Barbara Pro

Northwestern University

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place