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

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00369629
• Collaborator: National Cancer Institute (NCI) (NIH), Eli Lilly and Company (Industry)
• Enrollment: 14
• Location: 1
• Arms: 4
• Actual Duration (Months): 81.2
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Gemcitabine; Drug: Pemetrexed	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma
• Actual Study Start Date: Aug 28, 2006
• Actual Primary Completion Date: Jul 16, 2012
• Actual Study Completion Date: Jun 4, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 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.	Drug: 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.; Drug: 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.
Experimental: Cohort 2 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.	Drug: 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.; Drug: 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.
Experimental: Cohort 3 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.	Drug: 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.; Drug: 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.
Experimental: Cohort 4 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.	Drug: 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.; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)
• Eli Lilly and Company

Investigators

• Principal Investigator: Barbara Pro, MD, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00369629
• Other Study ID Numbers: NU 05H8; P30CA060553; STU00006771
• First Posted: Aug 29, 2006
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Northwestern University: 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
• Additional relevant MeSH terms: Mycoses; Lymphoma; Mycosis Fungoides; Sezary Syndrome; Gemcitabine; Pemetrexed

Study Results

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.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
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
COMPLETED	4	2	3	0
NOT COMPLETED	2	1	2	0
Period Title: Treated 2 Cycles/Reached First Response
STARTED	4	2	3	0
COMPLETED	4	2	2	0
NOT COMPLETED	0	0	1	0
Period Title: Treated 2 Cycles/Reached First Response
STARTED	4	2	2	0
COMPLETED	0	0	0	0
NOT COMPLETED	4	2	2	0
Period Title: Treated 2 Cycles/Reached First Response
STARTED	6	3	5	0
COMPLETED	4	1	2	0
NOT COMPLETED	2	2	3	0

Baseline Characteristics

Arm/Group Title	Gemcitabine and Pemetrexed Disodium
Arm/Group Description	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 Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 71.4%
>=65 years	4 28.6%
Sex: Female, Male (Count of Participants)
Female	5 35.7%
Male	9 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.1%
Not Hispanic or Latino	13 92.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 21.4%
White	11 78.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	14 100%

Outcome Measures

1. Primary Outcome

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.

Outcome Measure Data

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
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.
Measure Participants	6	3	5	0
Perforated sigmoid diverticulitis	1	0	0
Febrile neutropenia	0	0	1

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		2/3 (66.7%)		2/5 (40%)		0/0 (NaN)
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%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Gastrointestinal disorders
Perforated sigmoid diverticulitis	1/5 (20%)	1	0/3 (0%)	0	0/5 (0%)	0	0/0 (NaN)	0
Infections and infestations
Bacteremia CMV	1/5 (20%)	1	0/3 (0%)	0	0/5 (0%)	0	0/0 (NaN)	0
Febrile neutropenia	0/5 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/0 (NaN)	0
Pneumonia	1/5 (20%)	1	0/3 (0%)	0	0/5 (0%)	0	0/0 (NaN)	0
Line sepsis and neutropenia	1/5 (20%)	1	0/3 (0%)	0	0/5 (0%)	0	0/0 (NaN)	0
Other (Not Including 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	6/6 (100%)		3/3 (100%)		5/5 (100%)		0/0 (NaN)
Blood and lymphatic system disorders
Hemoglobin	6/6 (100%)		2/3 (66.7%)		4/5 (80%)		0/0 (NaN)
Neutrophils (neutropenia)	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Leukocytes (total white blood cells)	3/6 (50%)		1/3 (33.3%)		2/5 (40%)		0/0 (NaN)
Lymphopenia	5/6 (83.3%)		1/3 (33.3%)		4/5 (80%)		0/0 (NaN)
Platelets (thrombocytopenia)	4/6 (66.7%)		1/3 (33.3%)		2/5 (40%)		0/0 (NaN)
Edema, Limb	1/6 (16.7%)		0/3 (0%)		4/5 (80%)		0/0 (NaN)
Edema	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Edema, trunk/genital	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Cardiac disorders
Hypotension	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Tachycardia	1/6 (16.7%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Ear and labyrinth disorders
Otitis, external ear	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Eye disorders
Blurred vision	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Watery eye (epiphora, tearing)	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Gastrointestinal disorders
Anorexia	0/6 (0%)		1/3 (33.3%)		1/5 (20%)		0/0 (NaN)
Constipation	0/6 (0%)		1/3 (33.3%)		4/5 (80%)		0/0 (NaN)
Dehydration	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Diarrhea	0/6 (0%)		1/3 (33.3%)		3/5 (60%)		0/0 (NaN)
Heartburn/dyspepsia	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Nausea	2/6 (33.3%)		1/3 (33.3%)		2/5 (40%)		0/0 (NaN)
Stomach pain	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Taste alteration (dysgeusia)	1/6 (16.7%)		1/3 (33.3%)		1/5 (20%)		0/0 (NaN)
Vomiting	1/6 (16.7%)		0/3 (0%)		3/5 (60%)		0/0 (NaN)
Abdomen pain	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
General disorders
Fatigue	2/6 (33.3%)		3/3 (100%)		4/5 (80%)		0/0 (NaN)
Fever	1/6 (16.7%)		0/3 (0%)		3/5 (60%)		0/0 (NaN)
Insomnia	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Rigor/chills	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Sweating/diaphoresis	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Weight loss	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Pain NOS	0/6 (0%)		1/3 (33.3%)		1/5 (20%)		0/0 (NaN)
Immune system disorders
allergic rhinitis	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Infections and infestations
Infection	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Dermatitis	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Colitis, infectious	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Urinary tract infection	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Investigations
International normalized Ration of prothrombin time (INR)	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Metabolism and nutrition disorders
Alkaline phosphatase	4/6 (66.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
ALT increase	0/6 (0%)		2/3 (66.7%)		1/5 (20%)		0/0 (NaN)
AST increase	4/6 (66.7%)		2/3 (66.7%)		3/5 (60%)		0/0 (NaN)
Albumin, serum-low	4/6 (66.7%)		1/3 (33.3%)		5/5 (100%)		0/0 (NaN)
Bilirubin (hyperbilirubinemia)	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Creatinine	5/6 (83.3%)		1/3 (33.3%)		2/5 (40%)		0/0 (NaN)
Calcium, serum-high (hypercalcemia)	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Calcium, serum-low (hypocalcemia)	2/6 (33.3%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Glucose, serum-high (hyperglycemia)	4/6 (66.7%)		3/3 (100%)		4/5 (80%)		0/0 (NaN)
Glucose, Serum-low (hypoglycemia)	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Potassium, serum-low (hypokalemia)	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Sodium, serum-high (hypernatremia)	2/6 (33.3%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Sodium, serum low (hyponatremia)	1/6 (16.7%)		0/3 (0%)		2/5 (40%)		0/0 (NaN)
Musculoskeletal and connective tissue disorders
Limb pain	0/6 (0%)		0/3 (0%)		2/5 (40%)		0/0 (NaN)
Nervous system disorders
Sensory Neuropathy	0/6 (0%)		0/3 (0%)		2/5 (40%)		0/0 (NaN)
Mental status	1/6 (16.7%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Anxiety (mood alteration)	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Depression (mood alteration)	0/6 (0%)		1/3 (33.3%)		0/5 (0%)		0/0 (NaN)
Headache	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Renal and urinary disorders
Hemorrhage, GU: Urinary NOS	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Renal failure	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Reproductive system and breast disorders
Scrotum pain	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Urethra pain	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Shortness of breath (dyspnea)	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)
Tachypnea	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Skin and subcutaneous tissue disorders
Flushing	0/6 (0%)		0/3 (0%)		2/5 (40%)		0/0 (NaN)
Hair loss (alopecia)	0/6 (0%)		0/3 (0%)		2/5 (40%)		0/0 (NaN)
Pruritus/itching	4/6 (66.7%)		1/3 (33.3%)		1/5 (20%)		0/0 (NaN)
Cellulitis	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
MRSA	0/6 (0%)		0/3 (0%)		1/5 (20%)		0/0 (NaN)
Vascular disorders
Thrombosis	1/6 (16.7%)		0/3 (0%)		0/5 (0%)		0/0 (NaN)

Limitations/Caveats

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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.