Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00069238
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arm: 1
• Actual Duration (Months): 209.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkins lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkin s lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objectives:

Determine the toxicity of Alemtuzumab and etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy in untreated cluster of differentiation 52 (CD52)-expressing T and natural killer (NK) lymphoid malignancies.

Determine the maximum tolerated dose of Alemtuzumab administered in combination with EPOCH chemotherapy.

Determine in a preliminary fashion the anti-tumor activity of the combination of Alemtuzumab and EPOCH chemotherapy.

Eligibility:

CD52-expressing lymphoid malignancy.

Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Adequate organ function, unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart. failure within the past year.

Human immunodeficiency virus (HIV) negative.

Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in a preliminary fashion the antitumor activity of the combination with Dose-Adjusted EPOCH.

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each. Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed by dose-adjusted EPOCH chemotherapy days 1-5.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell	Biological: Alemtuzumab (Campath); Drug: EPOCH	Phase 2

Detailed Description

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkins lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkins lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objective:

Determine the toxicity and maximum tolerated dose (MTD) of Alemtuzumab and EPOCH chemotherapy in untreated cluster of differentiation 52 (CD52)-expressing T and natural killer (NK) lymphoid malignancies

Eligibility:

• CD52-expressing lymphoid malignancy.

• Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

• Age greater than or equal to 17 years.

• Adequate organ function, unless impairment due to respective organ involvement by tumor.

• No active symptomatic ischemic heart disease, myocardial infarction or congestive heart. failure within the past year.

• Human immunodeficiency virus (HIV) negative.

• Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in a preliminary fashion the antitumor activity of the combination with Dose-Adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH).

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each. Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed by dose-adjusted EPOCH chemotherapy days 1-5.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial of Alemtuzumab and Dose-Adjusted Epoch in Chemotherapy Naive Aggressive T and NK-Cell Lymphomas
• Actual Study Start Date: Sep 19, 2003
• Actual Primary Completion Date: Jun 11, 2009
• Actual Study Completion Date: Mar 17, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Alemtuzumab Dose Escalation Alemtuzumab (Campath) followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) every 3 weeks for up to 6 cycles. Three cohorts of 3 to 6 patients will be treated. Cohort 1 will receive 30mg of Alemtuzumab, cohort 2 will receive 60mg of Alemtuzumab, and cohort 3 will receive 90mg of Alemtuzumab. If 1 of 3 participants entered at a given dose level experiences dose limiting toxicity (DLT), up to 3 additional participants will be entered at that dose level. If 2 of 6 participants experience DLT at a particular dose level, the maximum tolerated dose (MTD) has been exceeded. The preceding dose level will be the MTD, provided 6 participants have been entered at this level and no more than 1 has experienced DLT.

Biological: Alemtuzumab (Campath); Alemtuzumab (Campath) followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) every 3 weeks for up to 6 cycles.; Other Names: Campath ; Drug: EPOCH; Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) + Alemtuzumab (Campath) every 3 weeks for up to 6 cycles.; Other Names: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Alemtuzumab [up to 2 cycles of therapy, approximately 42 days]

   MTD was achieved by increasing doses of Alemtuzumab on three cohorts. Cohort 1 received 30mg of Alemtuzumab, cohort 2 received 60mg of Alemtuzumab, and cohort 3 received 90mg of Alemtuzumab intravenously up to 2 cycles. The MTD reflects the highest dose of Alemtuzumab in which no more than 1 of 6 participants entered at a specific dose level experienced a dose limiting toxicity (DLT).

2. Number of Participants With Adverse Events [67 months and 9 days]

   Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Secondary Outcome Measures

1. Clinical Response [From date of onstudy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 67 months and 9 days.]

   Response was measured by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (Cru)is as per complete remission criterion except that if a residual node is greater than 1.5cm, it must have decreased by greater than 75% in the sum of the products of the perpendicular diameters (SPD). Partial response (PR) is ≥50% decrease in the SPD of 6 largest dominant nodes or nodal masses. Progressive disease (PD) is ≥50% increase from the nadir in the SPD of any previously identified abnormal node for PRS or non-responders. Stable disease (SD) is less than a PR but not progressive disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• ELIGIBILITY CRITERIA:

Cluster of differentiation 52 (CD52)-expressing lymphoid malignancy, confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, National Cancer Institute (NCI). Patients with T & natural killer (NK) cell malignancy without accessible tissue for flow cytometry analysis may be treated on this study.

Patients with chemotherapy naive aggressive T & NK lymphomas, including but not limited to peripheral T cell lymphoma (not otherwise specified (nos)), gamma-delta hepatosplenic T cell lymphoma, subcutaneous panniculitis-like T cell, NK-T cell lymphoma confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Laboratory tests: Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min; bilirubin less than 2.0 mg/dl unless due to Gilbert's, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times upper limit of normal (ULN) (AST and ALT is less than or equal to 6 times ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) and; absolute neutrophil count (ANC) is greater than or equal to 1000/mm(3), platelet greater than or equal to 75,000/mm(3); unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year.

Human immunodeficiency virus (HIV) negative, because of the unknown effects of combined therapy with chemotherapy and an immunosuppressive agent on HIV progression.

Signed informed consent.

Willing to use contraception.

Not pregnant or nursing, because of the unknown effects of Alemtuzumab on the developing fetus and infant.

No serious underlying medical condition or infection that would contraindicate treatment. Patients with central nervous system (CNS) involvement are eligible for treatment on this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Wyndham H Wilson, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 16, 2018
• Informed Consent Form - May 21, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun 1;89(11):3909-18.
• Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361-92. Review.
• Wing MG, Moreau T, Greenwood J, Smith RM, Hale G, Isaacs J, Waldmann H, Lachmann PJ, Compston A. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. J Clin Invest. 1996 Dec 15;98(12):2819-26.

• Responsible Party: Wyndham Wilson, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00069238
• Other Study ID Numbers: 030304; 03-C-0304; NCT00072254
• First Posted: Sep 18, 2003
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wyndham Wilson, M.D., Principal Investigator, National Cancer Institute (NCI): Lymphoma; T-Cell Lymphoma; NK -Cell Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell; Prednisone; Cyclophosphamide; Doxorubicin; Etoposide; Vincristine; Alemtuzumab

Study Results

Participant Flow

Arm/Group Title	Alemtuzumab 30 mg	Alemtuzumab 60 mg	Alemtuzumab 90 mg
Arm/Group Description	Alemtuzumab (Campath) 30mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.	Alemtuzumab (Campath) 60mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.	Alemtuzumab (Campath) 90mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.
Period Title: Cohort 1 - Dose Level 1 (Weeks 1 - 18)
STARTED	25	0	0
COMPLETED	16	0	0
NOT COMPLETED	9	0	0
Period Title: Cohort 1 - Dose Level 1 (Weeks 1 - 18)
STARTED	0	3	0
COMPLETED	0	1	0
NOT COMPLETED	0	2	0
Period Title: Cohort 1 - Dose Level 1 (Weeks 1 - 18)
STARTED	0	0	3
COMPLETED	0	0	1
NOT COMPLETED	0	0	2

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles.
Overall Participants	31
Age (Count of Participants)
<=18 years	1 3.2%
Between 18 and 65 years	27 87.1%
>=65 years	3 9.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.52 (15.5)
Sex: Female, Male (Count of Participants)
Female	16 51.6%
Male	15 48.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	31 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 6.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	15 48.4%
White	14 45.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	31 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Alemtuzumab
Description	MTD was achieved by increasing doses of Alemtuzumab on three cohorts. Cohort 1 received 30mg of Alemtuzumab, cohort 2 received 60mg of Alemtuzumab, and cohort 3 received 90mg of Alemtuzumab intravenously up to 2 cycles. The MTD reflects the highest dose of Alemtuzumab in which no more than 1 of 6 participants entered at a specific dose level experienced a dose limiting toxicity (DLT).
Time Frame	up to 2 cycles of therapy, approximately 42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles.
Measure Participants	31
Number [mg]	30

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame	67 months and 9 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles.
Measure Participants	31
Count of Participants [Participants]	31 100%

3. Secondary Outcome

Title	Clinical Response
Description	Response was measured by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (Cru)is as per complete remission criterion except that if a residual node is greater than 1.5cm, it must have decreased by greater than 75% in the sum of the products of the perpendicular diameters (SPD). Partial response (PR) is ≥50% decrease in the SPD of 6 largest dominant nodes or nodal masses. Progressive disease (PD) is ≥50% increase from the nadir in the SPD of any previously identified abnormal node for PRS or non-responders. Stable disease (SD) is less than a PR but not progressive disease.
Time Frame	From date of onstudy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 67 months and 9 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles. The adverse events are not reported per dose level because we normally look at all adverse events together irrespective of the dose level.
Measure Participants	31
Complete Response	17 54.8%
Complete Response Unconfirmed	0 0%
Partial Response	7 22.6%
Progressive Disease	2 6.5%
Stable Disease	1 3.2%
Not Evaluable	4 12.9%

Adverse Events

Time Frame	67 months and 9 days
Arm/Group Title	All Participants
Arm/Group Description	All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles. The adverse events are not reported per dose level because we normally look at all adverse events together irrespective of the dose level.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	23/31 (74.2%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	23/31 (74.2%)
Blood and lymphatic system disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Upper GI Not otherwise specified (NOS)	1/31 (3.2%)	1
General disorders
DEATH:: Death related to the study	7/31 (22.6%)	7
DEATH:: Death due to progression	16/31 (51.6%)	16
Infections and infestations
INFECTION:: Febrile neutropenia	1/31 (3.2%)	1
INFECTION:: Infection	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically)	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection with unknown ANC:: Blood	1/31 (3.2%)	1
Renal and urinary disorders
RENAL/GENITOURINARY:: Cystitis	1/31 (3.2%)	1
RENAL/GENITOURINARY:: Urinary frequency/urgency	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	31/31 (100%)
Blood and lymphatic system disorders
AUDITORY/EAR:: Otitis, middle ear (non-infectious)	1/31 (3.2%)	1
BLOOD/BONE MARROW:: Bone marrow cellularity	4/31 (12.9%)	4
BLOOD/BONE MARROW:: Hemoglobin	29/31 (93.5%)	101
BLOOD/BONE MARROW:: Leukocytes (total white blood count (WBC))	30/31 (96.8%)	121
BLOOD/BONE MARROW:: Lymphopenia	30/31 (96.8%)	74
BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC)	30/31 (96.8%)	116
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus bradycardia	1/31 (3.2%)	1
COAGULATION:: PTT (Partial Thromboplastin Time)	4/31 (12.9%)	5
GASTROINTESTINAL:: Mucositis/stomatitis (functional/symptomatic):: Esophagus	1/31 (3.2%)	1
LYMPHATICS:: Edema: head and neck	1/31 (3.2%)	1
LYMPHATICS:: Edema: limb	4/31 (12.9%)	4
LYMPHATICS:: Edema: trunk/genital	1/31 (3.2%)	1
Cardiac disorders
BLOOD/BONE MARROW:: Platelets	28/31 (90.3%)	102
CARDIAC ARRHYTHMIA:: Palpitations	2/31 (6.5%)	2
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus tachycardia	1/31 (3.2%)	1
CARDIAC ARRHYTHMIA:: Vasovagal episode	1/31 (3.2%)	1
CARDIAC GENERAL:: Hypertension	1/31 (3.2%)	1
CARDIAC GENERAL:: Hypotension	9/31 (29%)	14
Ear and labyrinth disorders
AUDITORY/EAR:: Tinnitus	1/31 (3.2%)	1
Eye disorders
OCULAR/VISUAL:: Ocular/Visual - Other (Specify, red eyes)	1/31 (3.2%)	1
OCULAR/VISUAL:: Ophthalmoplegia/diplopia (double vision)	1/31 (3.2%)	1
OCULAR/VISUAL:: Vision-blurred vision	3/31 (9.7%)	3
OCULAR/VISUAL:: Vision-photophobia	1/31 (3.2%)	1
OCULAR/VISUAL:: Watery eye (epiphora, tearing)	1/31 (3.2%)	1
PAIN:: Pain:: Eye	2/31 (6.5%)	2
OCULAR/VISUAL:: Ocular/Visual - Other (Specify, dilated, non-reactive R.pupil	1/31 (3.2%)	1
Gastrointestinal disorders
GASTROINTESTINAL:: Anorexia	11/31 (35.5%)	15
GASTROINTESTINAL:: Constipation	12/31 (38.7%)	14
GASTROINTESTINAL:: Dehydration	1/31 (3.2%)	1
GASTROINTESTINAL:: Dental: teeth	1/31 (3.2%)	1
GASTROINTESTINAL:: Diarrhea	14/31 (45.2%)	23
GASTROINTESTINAL:: Dry mouth/salivary gland (xerostomia)	2/31 (6.5%)	2
GASTROINTESTINAL:: Esophagitis	1/31 (3.2%)	1
GASTROINTESTINAL:: Flatulence	2/31 (6.5%)	2
GASTROINTESTINAL:: Gastritis (including bile reflux gastritis)	1/31 (3.2%)	1
GASTROINTESTINAL:: Gastrointestinal - Other (Specify, duodenitis)	1/31 (3.2%)	1
GASTROINTESTINAL:: Heartburn/dyspepsia	4/31 (12.9%)	4
GASTROINTESTINAL:: Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/31 (3.2%)	1
GASTROINTESTINAL:: Mucositis/stomatitis (clinical exam):: Oral cavity	20/31 (64.5%)	33
GASTROINTESTINAL:: Mucositis/stomatitis (clinical exam):: Pharynx	1/31 (3.2%)	1
GASTROINTESTINAL:: Mucositis/stomatitis (functional/symptomatic):: Oral cavity	7/31 (22.6%)	8
GASTROINTESTINAL:: Nausea	18/31 (58.1%)	38
GASTROINTESTINAL:: Proctitis	1/31 (3.2%)	1
GASTROINTESTINAL:: Taste alteration (dysgeusia)	4/31 (12.9%)	4
GASTROINTESTINAL:: Typhlitis (cecal inflammation)	1/31 (3.2%)	1
GASTROINTESTINAL:: Vomiting	13/31 (41.9%)	20
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Lower GI NOS	1/31 (3.2%)	1
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Oral cavity	1/31 (3.2%)	1
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Upper GI NOS	2/31 (6.5%)	2
INFECTION:: Infection - Other (Specify, BLOOD)	1/31 (3.2%)	1
PAIN:: Pain:: Abdomen Not otherwise specified (NOS)	7/31 (22.6%)	9
PAIN:: Pain:: Dental/teeth/peridontal	1/31 (3.2%)	1
PAIN:: Pain:: Rectum	1/31 (3.2%)	1
GASTROINTESTINAL:: Gastrointestinal - Other (Specify, tongue-blue spot)	1/31 (3.2%)	1
PAIN:: Pain - Other (Specify, Pain: jaw pain)	1/31 (3.2%)	1
PAIN:: Pain - Other (Specify, Pain:teeth)	1/31 (3.2%)	2
PAIN:: Pain - Other (Specify, Pain: tooth	1/31 (3.2%)	1
General disorders
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Supraventricular arrhythmia NOS	1/31 (3.2%)	1
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Supraventricular tachycardia	2/31 (6.5%)	2
CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)	18/31 (58.1%)	33
CONSTITUTIONAL SYMPTOMS	11/31 (35.5%)	16
CONSTITUTIONAL SYMPTOMS:: Insomnia	5/31 (16.1%)	5
CONSTITUTIONAL SYMPTOMS:: Rigors/chills	9/31 (29%)	14
CONSTITUTIONAL SYMPTOMS:: Sweating (diaphoresis)	4/31 (12.9%)	4
CONSTITUTIONAL SYMPTOMS:: Weight loss	7/31 (22.6%)	8
HEMORRHAGE/BLEEDING:: Hemorrhage/Bleeding - Other (Specify, R. neck after picc line)	1/31 (3.2%)	1
PAIN:: Pain - Other (Specify, L wrist)	1/31 (3.2%)	1
Immune system disorders
ALLERGY/IMMUNOLOGY:: Allergic reaction/hypersensitivity (including drug fever)	7/31 (22.6%)	11
ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	9/31 (29%)	11
Infections and infestations
INFECTION:: Infection(documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	2
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	4/31 (12.9%)	5
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	2
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	2
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	4/31 (12.9%)	4
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	5
INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Blood	1/31 (3.2%)	3
INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Oral cavity-gums (gingivitis)	1/31 (3.2%)	1
INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Skin (cellulitis)	1/31 (3.2%)	1
INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Urinary tract NOS	4/31 (12.9%)	4
INFECTION:: Infection with unknown ANC:: Oral cavity-gums (gingivitis)	1/31 (3.2%)	1
INFECTION:: Infection with unknown ANC:: Urinary tract NOS	1/31 (3.2%)	1
Metabolism and nutrition disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Nose	4/31 (12.9%)	5
INFECTION:: Febrile neutropenia	16/31 (51.6%)	28
METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)	14/31 (45.2%)	38
METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)	14/31 (45.2%)	29
METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)	20/31 (64.5%)	49
METABOLIC/LABORATORY:: Alkaline phosphatase	16/31 (51.6%)	22
METABOLIC/LABORATORY:: Amylase	1/31 (3.2%)	1
METABOLIC/LABORATORY:: Bicarbonate, serum-low	4/31 (12.9%)	6
METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)	10/31 (32.3%)	12
METABOLIC/LABORATORY:: Calcium, serum-high (hypercalcemia)	2/31 (6.5%)	2
METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)	19/31 (61.3%)	44
METABOLIC/LABORATORY:: Creatinine	3/31 (9.7%)	3
METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)	17/31 (54.8%)	47
METABOLIC/LABORATORY:: Glucose, serum-low (hypoglycemia)	6/31 (19.4%)	6
METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)	15/31 (48.4%)	30
METABOLIC/LABORATORY:: Magnesium, serum-low (hypomagnesemia)	18/31 (58.1%)	28
METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)	16/31 (51.6%)	26
METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)	9/31 (29%)	10
METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)	17/31 (54.8%)	26
METABOLIC/LABORATORY:: Sodium, serum-high (hypernatremia)	4/31 (12.9%)	4
METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)	16/31 (51.6%)	28
METABOLIC/LABORATORY:: Uric acid, serum-high (hyperuricemia)	5/31 (16.1%)	5
Musculoskeletal and connective tissue disorders
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	2/31 (6.5%)	2
INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Sinus	1/31 (3.2%)	1
INFECTION:: Infection with unknown ANC:: Blood	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Arthritis (non-septic)	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Joint-effusion	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Muscle weakness, generalized or specific area (not due to neuropathy)	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Muscle weakness, generalized or specific area (not due to neuropathy)	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Musculoskeletal/Soft Tissue - Other (Specify, __)	1/31 (3.2%)	1
MUSCULOSKELETAL/SOFT TISSUE:: Soft tissue necrosis:: Extremity-lower	1/31 (3.2%)	1
PAIN:: Pain:: Back	7/31 (22.6%)	9
PAIN:: Pain:: Bone	12/31 (38.7%)	20
PAIN:: Pain:: Buttock	1/31 (3.2%)	1
PAIN:: Pain:: Extremity-limb	1/31 (3.2%)	1
PAIN:: Pain:: Joint	5/31 (16.1%)	6
PAIN:: Pain:: Muscle	10/31 (32.3%)	11
PAIN:: Pain:: Neck	1/31 (3.2%)	1
PAIN:: Pain - Other (Specify, lumbar puncture (LP) site)	1/31 (3.2%)	1
PAIN:: Pain - Other (Specify, Pain L big toe	1/31 (3.2%)	1
Nervous system disorders
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/31 (3.2%)	1
NEUROLOGY:: Confusion	3/31 (9.7%)	3
NEUROLOGY:: Dizziness	9/31 (29%)	12
NEUROLOGY:: Laryngeal nerve dysfunction	1/31 (3.2%)	1
NEUROLOGY:: Mood alteration:: Agitation	1/31 (3.2%)	1
NEUROLOGY:: Mood alteration:: Anxiety	3/31 (9.7%)	3
NEUROLOGY:: Mood alteration:: Depression	1/31 (3.2%)	1
NEUROLOGY:: Neuropathy: motor	3/31 (9.7%)	3
NEUROLOGY:: Neuropathy: sensory	24/31 (77.4%)	24
NEUROLOGY:: Somnolence/depressed level of consciousness	1/31 (3.2%)	1
NEUROLOGY:: Syncope (fainting)	2/31 (6.5%)	2
NEUROLOGY:: Tremor	1/31 (3.2%)	1
PAIN:: Pain:: Head/headache	13/31 (41.9%)	22
Renal and urinary disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Bladder	1/31 (3.2%)	1
HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Urinary NOS	1/31 (3.2%)	1
PAIN:: Pain:: Bladder	1/31 (3.2%)	1
RENAL/GENITOURINARY:: Cystitis	6/31 (19.4%)	6
RENAL/GENITOURINARY:: Incontinence, urinary	1/31 (3.2%)	1
RENAL/GENITOURINARY:: Obstruction, GU:: Ureter	1/31 (3.2%)	1
RENAL/GENITOURINARY:: Urinary frequency/urgency	5/31 (16.1%)	6
Reproductive system and breast disorders
PAIN:: Pain - Other (Specify, Pain:groin)	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Bronchopulmonary NOS	1/31 (3.2%)	1
PAIN:: Pain:: Chest/thorax NOS	5/31 (16.1%)	6
PAIN:: Pain:: Throat/pharynx/larynx	1/31 (3.2%)	2
PULMONARY/UPPER RESPIRATORY:: Bronchospasm, wheezing	1/31 (3.2%)	1
PULMONARY/UPPER RESPIRATORY:: Cough	7/31 (22.6%)	8
PULMONARY/UPPER RESPIRATORY:: Dyspnea (shortness of breath)	6/31 (19.4%)	8
PULMONARY/UPPER RESPIRATORY:: Hypoxia	2/31 (6.5%)	2
PULMONARY/UPPER RESPIRATORY:: Nasal cavity/paranasal sinus reactions	1/31 (3.2%)	1
PULMONARY/UPPER RESPIRATORY:: Pleural effusion (non-malignant)	2/31 (6.5%)	3
PULMONARY/UPPER RESPIRATORY:: Pneumonitis/pulmonary infiltrates	1/31 (3.2%)	1
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN:: Bruising (in absence of Grade 3 or 4 thrombocytopenia)	1/31 (3.2%)	1
DERMATOLOGY/SKIN:: Dermatology/Skin - Other (Specify, excoriation)	1/31 (3.2%)	1
DERMATOLOGY/SKIN:: Dry skin	1/31 (3.2%)	1
DERMATOLOGY/SKIN:: Flushing	1/31 (3.2%)	1
DERMATOLOGY/SKIN:: Hair loss/alopecia (scalp or body)	15/31 (48.4%)	15
DERMATOLOGY/SKIN:: Hyperpigmentation	2/31 (6.5%)	2
DERMATOLOGY/SKIN:: Injection site reaction/extravasation changes	1/31 (3.2%)	1
DERMATOLOGY/SKIN:: Nail changes	5/31 (16.1%)	5
DERMATOLOGY/SKIN:: Pruritus/itching	3/31 (9.7%)	4
DERMATOLOGY/SKIN:: Rash/desquamation	9/31 (29%)	12
DERMATOLOGY/SKIN:: Skin breakdown/decubitus ulcer	1/31 (3.2%)	1
HEMORRHAGE/BLEEDING:: Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	1/31 (3.2%)	1
Vascular disorders
VASCULAR:: Phlebitis (including superficial thrombosis)	1/31 (3.2%)	1
VASCULAR:: Thrombosis/embolism (vascular access-related)	3/31 (9.7%)	3
VASCULAR:: Thrombosis/thrombus/embolism	5/31 (16.1%)	5

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT 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.