Anti-Tac(Fv)-PE38 (LMB-2) to Treat Chronic Lymphocytic Leukemia

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00077922
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 94
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating chronic lymphocytic leukemia (CLL) in patients who have a protein called cluster of differentiation 25 (CD25) on their cancer cells. LMB-2 is a recombinant immunotoxin. It is made up of two parts: a genetically engineered monoclonal antibody that binds to cancer cells with CD25 on their surface, and a toxin produced by bacteria that kills the cancer cells to which it binds. LMB-2 has killed CD 25-containing cells in laboratory experiments and has caused tumors in mice to shrink. Preliminary studies in humans have shown some effectiveness in shrinking tumors in patients with various types of lymph and blood cancers.

Patients 18 years of age and older with CLL who have CD25 receptor proteins on their cancer cells and whose disease has progressed within 2 years of treatment with fludarabine may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), echocardiogram, chest x-ray, computed tomography (CT) scans of the chest, abdomen and pelvis, and a bone marrow biopsy.

Participants receive up to six cycles of LMB-2 therapy. Each 28-day cycle consists of 30-minute infusions of LMB-2 on cycle days 1, 3, and 5. The drug is infused through an intravenous (IV) catheter (plastic tube placed in a vein) or a central venous line-an IV tube placed in a large vein in the neck or chest that leads to the heart. Patients are admitted to the National Institutes of Health (NIH) Clinical Center for the first treatment cycle. If the infusion is well tolerated, subsequent cycles may be given on an outpatient basis. In addition to drug therapy, patients undergo the following procedures:

• Blood draws: Blood is drawn before, during, and after each LMB-2 infusion to measure blood levels of the drug, evaluate its effects on the cancer cells, and monitor side effects. Blood tests are also done before and during each cycle to determine how the immune system is interacting with the drug.

• Disease evaluations: Patients undergo a physical examination, blood tests, chest x-ray, and EKG before each treatment cycle and at follow-up visits. With the patient's permission, CT scans, echocardiogram, and bone marrow biopsies may be repeated before some treatment cycles if these tests prove useful in evaluating the disease response to LMB-2.

Patients may receive up to six cycles of LMB-2 as long as their cancer does not worsen and they do not develop serious side effects. At the end of the treatment cycles, patients will have blood tests done weekly by their local physician, and the results will be sent to the NCI study investigators.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphocytic; Chronic	Drug: LMB-2	Phase 2

Detailed Description

Background:

It is estimated that 30-50% of patients with CLL have tumors that express cluster of differentiation 25 (CD25) (Tac or IL2R). Normal resting T-cells are not sensitive to LMB-2 due to insufficient CD25 expression. LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of MAb anti-Tac and truncated Pseudomonas exotoxin. A phase I trial at National Cancer Institute (NCI) found that the maximum tolerated dose (MTD) of LMB-2 was 40 microg/Kg IV given every other day for 3 doses (every other day (QOD) x3) with prophylactic IV fluid. The most common adverse events were transient fever, hypoalbuminemia and transaminase elevations. In that trial, one of eight patients with chronic lymphocytic leukemia had a partial remission. The other seven CLL patients had stable disease. In addition, four of four patients with hairy cell leukemia had responses (1 complete response (CR), 3 partial response (PRs)) and 3 other patients had PRs (1 cutaneous T-cell lymphoma (CTCL), 1 healthy donor (HD), 1 acute T-cell leukemia/lymphoma (ATL)). Because LMB-2 is cytotoxic to cells expressing CD25, CD25+ CLL patients are good candidates for further testing with LMB-2.

Objectives:

The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB- 2) in patients with Tac-expressing Chronic Lymphocytic Leukemia (CLL). The primary endpoint of this trial is response rate. We will also evaluate response duration, LMB-2 immunogenicity, pharmacokinetics, toxicity, and monitor soluble Tac levels in the serum.

Eligibility:

CD25 positive CLL or prolymphocytic leukemia (PLL) confirmed by flow cytometry of blood, with either lymphadenopathy, splenomegaly, hepatomegaly, hemoglobin less than 11 g/dl,

or platelets less than 100,000/ul.

Patients must have progression following purine analog or alkylating agent.

Labs required: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5- time upper limit,

albumin greater than or equal to 3, bilirubin less than equal to 2.2 (unless unconjugated greater than or equal to 80%)

and creatinine less than or equal to 1.4 (unless creatinine clearance greater than or equal to 50 ml/min).

Design:

Patients receive LMB-2 40 ug/Kg QOD x3 every 4 weeks in absence of neutralizing antibodies or progressive disease. 1st stage is 16 patients, to expand to 25 if greater than 1 of 16 patients respond.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia
• Actual Study Start Date: Feb 29, 2004
• Actual Primary Completion Date: Dec 31, 2011
• Actual Study Completion Date: Dec 31, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LMB-2 in chronic lymphocytic leukemia 40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.	Drug: LMB-2; 40 micrograms/kg every other day (QOD) x 3 every 4 weeks

Outcome Measures

Primary Outcome Measures

1. Response Rate [Patients were followed for at least 30 days after last treatment. Because the study allows 6 treatment cycles, this can be up to 7 months.]

   Response is measured by the 1996 National Cancer Institute (NCI) Working Group Criteria (NCIWG). Complete response is defined as no hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must resolve to <1.0cm of 1-1.5cm at baseline, or <1.5cm if >1.5cm at baseline. Partial response is >=50% decrease in peripheral blood lymphocytes count from the pretreatment baseline value. Progressive disease is >=50% increase in the sum of the products of the greatest perpendicular dimensions of a t least 2 lymph nodes on two consecutive examinations 2 weeks apart (at least 1 node must be >=2cm) or appearance of new palpable lymph nodes. Stable disease is characterized by not meeting the above criteria. For additional details about the NCIWG, see the protocol link module.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [54 months]

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

Eligibility Criteria

Criteria

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

• INCLUSION CRITERIA:

Patients must have histopathological evidence of CD25+ CLL or prolymphocytic leukemia (PLL) confirmed by the NIH pathology department. This requires that at least 50% of the peripheral malignant lymphocytes be CD25 positive by fluorescence activated cell sorting (FACS) with anti-CD25 antibody. Positive expression in a FACS assay is defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody by FACS, or greater than 400 CD25 sites/cell by FACS or radiolabeled binding assay.

In the three stage modified Rai system, patients must be intermediate or high risk. This means they must have circulating CLL cells and at least one of the following: lymphadenopathy, splenomegaly, hepatomegaly, anemia (Hgb less than 11g/dL), or thrombocytopenia (Plt less than 100,000/ul).

Patients must have had progressive disease after prior standard therapy containing either a purine analog or an alkylating agent.

Patients must not have received systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic steroids (except stable doses of Prednisone less than or equal to 20 mg/day) within 4 weeks of enrollment.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

At least 18 years old.

Patients must be able to understand and give informed consent.

Female patients of childbearing potential must have a negative pregnancy test and all patients must use effective contraception (a barrier form of contraception).

The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must each be less than or equal to 2.5-times the upper limits of normal. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 2.2 mg/dL except in patients with Gilbert's syndrome (as defined by greater than 80% unconjugated bilirubin) it must be less than 5 mg/dl.

The creatinine must be less than or equal to 1.4 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min as measured from a 24-hour urine collection.

Patients should not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

EXCLUSION CRITERIA:

Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-lgG antibodies. No patient whose serum neutralizes greater than 75% of the activity of 1 micro g/mL of LMB-2 will be treated.

Patients who received LMB-2 on another trial.

Monoclonal antibody therapy within 12 weeks of enrollment.

Patients who are pregnant or breast-feeding.

Patients who are human immunodeficiency virus (HIV) positive.

Patients who have hepatitis C or chronic liver disease. Patients would not be excluded for hepatitis B surface antigen positivity if on Lamivudine.

Patients receiving warfarin for anticoagulation.

Patients with a left ventricular ejection fraction of less than the institutional lower limit of normal.

Patients with a carbon monoxide diffusing capacity (DLCO) less than 55% of normal or an forced expiratory volume 1 (FEV1) less than 60% of normal.

Patients who have active cancer requiring treatment.

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: Robert J Kreitman, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jul 5, 2011

More Information

Publications

• Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7.
• Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999 Dec;17(12):3835-49.
• Rai KR, Sawitsky A. A review of the prognostic role of cytogenetic, phenotypic, morphologic, and immune function characteristics in chronic lymphocytic leukemia. Blood Cells. 1987;12(2):327-38. Review.

• Responsible Party: Robert Kreitman, M.D., Dr. Robert Kreitman, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00077922
• Other Study ID Numbers: 040121; 04-C-0121; NCT00080821
• First Posted: Feb 13, 2004
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• 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 Robert Kreitman, M.D., Dr. Robert Kreitman, National Institutes of Health Clinical Center (CC): LMB-2; Chronic Lymphocytic Leukemia; CLL; Immunotoxin; Oncology; Lymphocytes; Hematological Disease; Monoclonal Antibody; Neutralizing Antibodies
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

Participant Flow

Arm/Group Title	LMB-2 in Chronic Lymphocytic Leukemia
Arm/Group Description	40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	LMB-2 in Chronic Lymphocytic Leukemia
Arm/Group Description	40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 60%
>=65 years	6 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.36 (7.6)
Sex: Female, Male (Count of Participants)
Female	5 33.3%
Male	10 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	14 93.3%
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	2 13.3%
White	13 86.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Response is measured by the 1996 National Cancer Institute (NCI) Working Group Criteria (NCIWG). Complete response is defined as no hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must resolve to <1.0cm of 1-1.5cm at baseline, or <1.5cm if >1.5cm at baseline. Partial response is >=50% decrease in peripheral blood lymphocytes count from the pretreatment baseline value. Progressive disease is >=50% increase in the sum of the products of the greatest perpendicular dimensions of a t least 2 lymph nodes on two consecutive examinations 2 weeks apart (at least 1 node must be >=2cm) or appearance of new palpable lymph nodes. Stable disease is characterized by not meeting the above criteria. For additional details about the NCIWG, see the protocol link module.
Time Frame	Patients were followed for at least 30 days after last treatment. Because the study allows 6 treatment cycles, this can be up to 7 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LMB-2 in Chronic Lymphocytic Leukemia
Arm/Group Description	40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.
Measure Participants	15
Complete Response	0 0%
Partial Response	1 6.7%
Progressive Disease	3 20%
Stable Disease	11 73.3%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LMB-2 in Chronic Lymphocytic Leukemia
Arm/Group Description	40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.
Measure Participants	15
Number [Participants]	15 100%

Adverse Events

Time Frame	54 months
Arm/Group Title	LMB-2 in Chronic Lymphocytic Leukemia
Arm/Group Description	40 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with chronic lymphocytic leukemia, the most prevalent form of adult leukemia.
All Cause Mortality
	LMB-2 in Chronic Lymphocytic Leukemia
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	LMB-2 in Chronic Lymphocytic Leukemia
	Affected / at Risk (%)	# Events
Total	7/15 (46.7%)
Blood and lymphatic system disorders
Platelets	1/15 (6.7%)	1
Cardiac disorders
Cardiac-ischemia/infarction	1/15 (6.7%)	1
Cardiac troponin I (cTnI)	1/15 (6.7%)	1
Hypotension	1/15 (6.7%)	1
Eye disorders
Ocular/Visual-Other (Specify, blindness r/t CVA)	1/15 (6.7%)	1
Infections and infestations
Infection	1/15 (6.7%)	1
Infection (documented clinically or microbiologically)	2/15 (13.3%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)	1/15 (6.7%)	1
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)	1/15 (6.7%)	1
Potassium, serum-low (hypokalemia)	1/15 (6.7%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/15 (6.7%)	1
Confusion	1/15 (6.7%)	1
Renal and urinary disorders
Obstruction, GU: Ureter	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/15 (13.3%)	2
Other (Not Including Serious) Adverse Events
	LMB-2 in Chronic Lymphocytic Leukemia
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
haptoglobin	2/15 (13.3%)	5
Hemoglobin	9/15 (60%)	71
Leukocytes (total WBC)	1/15 (6.7%)	4
Neutrophils/granulocytes (ANC/AG)	8/15 (53.3%)	30
Platelets	7/15 (46.7%)	48
fibrinogen	1/15 (6.7%)	1
PTT (Partial Thromboplastin Time)	1/15 (6.7%)	1
Edema: limb	10/15 (66.7%)	19
Edema::head and neck	6/15 (40%)	14
Cardiac disorders
Supraventricular and nodal arrhythmia::Sinus tachycardia	3/15 (20%)	3
Hypotension	3/15 (20%)	4
Pericardial effusion (non-malignant)	3/15 (20%)	3
Ear and labyrinth disorders
Pain::Middle ear	1/15 (6.7%)	1
Endocrine disorders
Thyroid function, low (hypothyroidism)	2/15 (13.3%)	2
Eye disorders
Dry eye syndrome	2/15 (13.3%)	2
Ocular surface disease	2/15 (13.3%)	2
Vision-blurred vision	1/15 (6.7%)	1
Pain::Eye	1/15 (6.7%)	1
Gastrointestinal disorders
Anorexia	2/15 (13.3%)	2
Constipation	3/15 (20%)	3
Dehydration	1/15 (6.7%)	1
Diarrhea	3/15 (20%)	3
Distension/bloating, abdominal	1/15 (6.7%)	1
Dysphagia (difficulty swallowing)	2/15 (13.3%)	2
Heartburn/dyspepsia	2/15 (13.3%)	2
Mucositis/stomatitis (clinical exam)::Oral cavity	1/15 (6.7%)	1
Nausea	6/15 (40%)	12
Taste alteration (dysgeusia)	1/15 (6.7%)	2
Vomiting	4/15 (26.7%)	6
Hemorrhage, GI::Oral cavity	1/15 (6.7%)	1
Pain: Abdomen NOS	1/15 (6.7%)	1
Pain::Dental/teeth/peridontal	1/15 (6.7%)	1
Pain::Oral cavity	2/15 (13.3%)	2
General disorders
Fatigue (asthenia, lethargy, malaise)	7/15 (46.7%)	13
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	11/15 (73.3%)	23
Insomnia	3/15 (20%)	3
Rigors/chills	3/15 (20%)	4
Sweating (diaphoresis)	2/15 (13.3%)	2
Weight gain	9/15 (60%)	15
Weight loss	1/15 (6.7%)	1
Flu-like symptoms	2/15 (13.3%)	2
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/15 (6.7%)	1
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2/15 (13.3%)	2
Infections and infestations
Febrile neutropenia	1/15 (6.7%)	1
Infection (documented clinically or microbiologically)	1/15 (6.7%)	1
Infection (documented clinically or microbiologically)	1/15 (6.7%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lip/perioral	2/15 (13.3%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Oral cavity-gums (gingivitis)	3/15 (20%)	7
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus	2/15 (13.3%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS	2/15 (13.3%)	2
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	4/15 (26.7%)	10
AST, SGOT(serum glutamic oxaloacetic transaminase)	11/15 (73.3%)	49
Albumin, serum-low (hypoalbuminemia)	14/15 (93.3%)	72
Alkaline phosphatase	6/15 (40%)	19
Amylase	3/15 (20%)	4
Bicarbonate, serum low	2/15 (13.3%)	4
Bilirubin (hyperbilirubinemia)	5/15 (33.3%)	13
CPK (creatine phosphokinase)	3/15 (20%)	7
Calcium, serum-high (hypercalcemia)	1/15 (6.7%)	1
Calcium, serum-low (hypocalcemia)	3/15 (20%)	11
Cholesterol, serum-high (hypercholesteremia)	2/15 (13.3%)	4
Creatinine	4/15 (26.7%)	8
GGT (gamma-Glutamyl transpeptidase)	3/15 (20%)	5
Glucose, serum-high (hyperglycemia)	7/15 (46.7%)	12
Glucose, serum-low (hypoglycemia)	3/15 (20%)	8
Hemoglobinuria	3/15 (20%)	3
Lipase	2/15 (13.3%)	2
Magnesium, serum-high (hypermagnesemia)	6/8 (75%)	12
Magnesium, serum-low (hypomagnesemia)	8/15 (53.3%)	26
Phosphate, serum-high (hyperphosphatemia)	7/15 (46.7%)	17
Potassium, serum-high (hyperkalemia)	4/15 (26.7%)	9
Potassium, serum-low (hypokalemia)	5/15 (33.3%)	22
Proteinuria	3/15 (20%)	3
Sodium, serum-high (hypernatremia)	5/15 (33.3%)	6
Sodium, serum-low (hyponatremia)	7/15 (46.7%)	25
Triglyceride, serum-high (hypertriglyceridemia)	3/15 (20%)	4
Uric acid, serum-high (hyperuricemia)	3/15 (20%)	3
Musculoskeletal and connective tissue disorders
Pain - Other (Specify, extremity, limb)	1/15 (6.7%)	1
Pain: Back	2/15 (13.3%)	3
Pain::Bone	1/15 (6.7%)	1
Pain: Extremity-limb	1/15 (6.7%)	1
Pain::Muscle	6/15 (40%)	9
Pain::Neck	1/15 (6.7%)	1
Nervous system disorders
Confusion	1/15 (6.7%)	2
Dizziness	6/15 (40%)	9
Mood alteration::Anxiety	1/15 (6.7%)	1
Mood alteration::Depression	1/15 (6.7%)	1
Neurology-Other (Specify, dizziness)	1/15 (6.7%)	1
Neuropathy:sensory	1/15 (6.7%)	1
Speech impairment (e.g., dysphasia or aphasia)	1/15 (6.7%)	1
Tremor	1/15 (6.7%)	1
Pain::Head/headache	7/15 (46.7%)	11
Pain::Neuralgia/peripheral nerve	2/15 (13.3%)	2
Renal and urinary disorders
Hemorrhage, GU: Bladder	1/15 (6.7%)	1
Hemorrhage, GU: Urinary NOS	6/15 (40%)	8
Urinary frequency/urgency	2/15 (13.3%)	2
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory: Lung	1/15 (6.7%)	1
Hemorrhage, pulmonary/upper respiratory: Nose	2/15 (13.3%)	2
Pain::Chest wall	2/15 (13.3%)	3
Pain::Throat/pharynx/larynx	1/15 (6.7%)	1
Atelectasis	2/15 (13.3%)	2
Cough	6/15 (40%)	7
Dyspnea (shortness of breath)	4/15 (26.7%)	5
Hypoxia	1/15 (6.7%)	1
Pleural effusion (non-malignant)	5/15 (33.3%)	6
Pneumonitis/pulmonary infiltrates	1/15 (6.7%)	2
Bladder spasms	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	5/15 (33.3%)	5
Dermatology/Skin - Other (Specify)	1/15 (6.7%)	1
Dry skin	1/15 (6.7%)	1
Rash/desquamation	2/15 (13.3%)	2
Rash: hand-foot skin reaction	1/15 (6.7%)	1
Ulceration	1/15 (6.7%)	1
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	2/15 (13.3%)	2
Vascular disorders
Acute vascular leak syndrome	7/15 (46.7%)	12
Phlebitis (including superficial thrombosis)	1/15 (6.7%)	1
Thrombosis/embolism (vascular access-related)	1/15 (6.7%)	1
Thrombosis/thrombus/embolism	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

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.