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

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

Pemetrexed

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00369629

First Posted

August 24, 2006

Last Updated

August 20, 2019

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI), Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00369629

Brief Title

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

Official Title

Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Terminated

Why Stopped

This was planned as a phase I/II study originally, but due to a lack of funding, the phase II portion was never conducted.

Study Start Date

August 28, 2006 (Actual)

Primary Completion Date

July 16, 2012 (Actual)

Study Completion Date

June 4, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI), Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: Determine the safety and tolerability of gemcitabine hydrochloride and pemetrexed disodium in patients with advanced mycosis fungoides or Sézary syndrome. (Phase I) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 4

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barbara Pro, MD

Organizational Affiliation

Robert H. Lurie Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-3013

Country

United States

Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

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