Lymphoma
Conditions
Keywords
recurrent mycosis fungoides/Sezary syndrome, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with pemetrexed disodium may kill more cancer cells. PURPOSE: This was planned as a phase I/II trial studying the side effects and determining the best dose of gemcitabine hydrochloride when given together with pemetrexed disodium. Unfortunately, due to a lack of funding, the phase II portion was never conducted.
Detailed description
OBJECTIVES: 1. Determine the safety and tolerability of gemcitabine hydrochloride and pemetrexed disodium in patients with advanced mycosis fungoides or Sézary syndrome. (Phase I) 2. Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with pemetrexed disodium in these patients. (Phase I) OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride. Originally, this was designed to be followed by a phase II portion to determine the efficacy in this population. Unfortunately, due to a lack of funding, the phase II portion was never conducted. During Phase I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≥ 2 of 6 patients experience dose-limiting toxicity.
Interventions
DRUGGemcitabine
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.
DRUGPemetrexed
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.
Sponsors
National Cancer Institute (NCI)
Eli Lilly and Company
Northwestern University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed\* mycosis fungoides or Sézary syndrome * Stage IB-IVB disease NOTE: \*Pathology report must read diagnostic or consistent with mycosis fungoides/Sézary syndrome * Failed ≥ 1 prior systemic treatment * Measurable disease * At least 1 indicator lesion must be designated prior to study entry PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 6 months * Creatinine ≤ 2.0 mg/dL * Creatinine clearance ≥ 45 mL/min * Bilirubin ≤ 2.2 mg/dL * AST and ALT ≤ 2 times upper limit of normal * WBC ≥ 3,000/mm³ * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * No acute infection requiring systemic treatment * No history of severe hypersensitivity reaction to the study drugs or to any other ingredient used in their formulation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 4 weeks since prior topical therapy, systemic chemotherapy, or biological therapy * No acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 days before and for 2 days after pemetrexed disodium infusion (5 days before and for 2 days after pemetrexed disodium infusion for patients taking NSAIDs with a long half-life \[e.g., naproxen, refocoxib, or celecoxib\]) * No concurrent topical agents except emollients * No other concurrent topical or systemic anticancer therapies * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | From the day that the first treatment is given through the first 28 day period for each patient. | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine and Pemetrexed Disodium 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. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Completed 4 More Cycles | Progressive disease | 2 | 1 | 2 | 0 |
| Completed 4 More Cycles | Withdrawal by Subject | 2 | 1 | 0 | 0 |
| Follow up for 1 Year | Death | 2 | 1 | 1 | 0 |
| Follow up for 1 Year | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Follow up for 1 Year | stopped being followed as study closed | 0 | 0 | 2 | 0 |
| Moved on to 4 More Cycles | Progressive Disease | 0 | 0 | 1 | 0 |
| Treated 2 Cycles/Reached First Response | Adverse Event | 0 | 0 | 1 | 0 |
| Treated 2 Cycles/Reached First Response | Physician Decision | 0 | 1 | 1 | 0 |
| Treated 2 Cycles/Reached First Response | Progressive disease | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Gemcitabine and Pemetrexed Disodium |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 14 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 2 / 3 | 2 / 5 | 0 / 0 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 5 / 5 | 0 / 0 |
| serious Total, serious adverse events | 2 / 5 | 0 / 3 | 1 / 5 | 0 / 0 |
Outcome results
Primary
Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort.
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.
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Perforated sigmoid diverticulitis | 1 DLT |
| Cohort 1 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Febrile neutropenia | 0 DLT |
| Cohort 2 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Perforated sigmoid diverticulitis | 0 DLT |
| Cohort 2 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Febrile neutropenia | 0 DLT |
| Cohort 3 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Perforated sigmoid diverticulitis | 0 DLT |
| Cohort 3 | Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort. | Febrile neutropenia | 1 DLT |