Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Advanced Myeloid Cancer

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00014495
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1
• Duration (Months): 109
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining chemotherapy and monoclonal antibody therapy in treating patients who have advanced myeloid cancer.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms	Biological: filgrastim; Drug: cytarabine; Radiation: bismuth Bi213 monoclonal antibody M195	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.

• Determine the antileukemic effects of this treatment in this patient population.

• Determine the toxicity of this treatment in this patient population.

• Determine the complete remission rate of patients treated with this treatment regimen.

OUTLINE: This is a dose escalation study of bismuth Bi 213 monoclonal antibody M195 (Bi213 MOAB M195).

Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.

Patients are followed twice weekly for 4 weeks and then monthly for 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies
• Study Start Date: Nov 1, 2000
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: bismuth Bi 213 monoclonal antibody M195 & cytarabine Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD. Patients are followed twice weekly for 4 weeks and then monthly for 3 months

Biological: filgrastim; Drug: cytarabine; Radiation: bismuth Bi213 monoclonal antibody M195

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose [2 years]

   The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

• Pathologically confirmed acute myeloid leukemia (AML) meeting one of the following criteria:

• Newly diagnosed AML, over age 60, and not eligible for higher priority protocols

• Newly diagnosed AML and unable to receive anthracycline-containing or high-dose cytarabine-containing regimens

• AML in relapse

• AML refractory to two courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy

• Chronic myelogenous leukemia in accelerated phase or myeloid blast crisis

• Refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocytic leukemia

• More than 25% of bone marrow blasts must be CD33 positive

• Not a candidate for immediate bone marrow transplantation with a HLA-compatible donor

• No active CNS leukemia

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 mg/dL (unless due to leukemia or Gilbert's disease)

• Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN)

• AST no greater than 2.5 times ULN

Renal:

• Creatinine less than 2 mg/dL OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV cardiac disease

Pulmonary:

• No pulmonary disease

Other:

• No detectable antibodies to monoclonal antibody M195

• No serious active uncontrolled infection

• No other concurrent active malignancy requiring therapy

• No other serious or life-threatening conditions that would preclude study

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior biologic therapy and recovered

Chemotherapy:

• See Disease Characteristics

• Prior hydroxyurea allowed if discontinued before study treatment

• At least 3 weeks since other prior chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan - Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Joseph G. Jurcic, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00014495
• Other Study ID Numbers: 00-117; MSKCC-00117; NCI-H01-0071
• First Posted: Jan 27, 2003
• Last Update Posted: Jan 22, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; untreated adult acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes
• Additional relevant MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Cytarabine; Bismuth; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Bismuth-labeled HuM195 (0.5 mCi/kg)	Bismuth-labeled HuM195 (0.75 mCi/kg)	Bismuth-labeled HuM195 (1 mCi/kg)	Bismuth-labeled HuM195 (1.25 mCi/kg)
Arm/Group Description	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.
Period Title: Overall Study
STARTED	3	3	20	6
COMPLETED	3	3	19	5
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	Bismuth-labeled HuM195 (0.5 mCi/kg)	Bismuth-labeled HuM195 (0.75 mCi/kg)	Bismuth-labeled HuM195 (1 mCi/kg)	Bismuth-labeled HuM195 (1.25 mCi/kg)	Total
Arm/Group Description	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.	Total of all reporting groups
Overall Participants	3	3	20	6	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	2 66.7%	9 45%	1 16.7%	14 43.8%
>=65 years	1 33.3%	1 33.3%	11 55%	5 83.3%	18 56.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	8 40%	1 16.7%	10 31.3%
Male	3 100%	2 66.7%	12 60%	5 83.3%	22 68.8%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	20 100%	6 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose
Description	The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bismuth Bi 213 Monoclonal Antibody M195 & Cytarabine
Arm/Group Description	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD. Patients are followed twice weekly for 4 weeks and then monthly for 3 months filgrastim cytarabine bismuth Bi213 monoclonal antibody M195
Measure Participants	20
Number [mCi/kg]	1

Adverse Events

Arm/Group Title	Bismuth-labeled HuM195 (0.5 mCi/kg)		Bismuth-labeled HuM195 (0.75 mCi/kg)		Bismuth-labeled HuM195 (1 mCi/kg)		Bismuth-labeled HuM195 (1.25 mCi/kg)
Arm/Group Description	Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.		Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.		Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.		Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 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. Once the MTD is determined, subsequent patients are treated at the MTD.
All Cause Mortality
	Bismuth-labeled HuM195 (0.5 mCi/kg)		Bismuth-labeled HuM195 (0.75 mCi/kg)		Bismuth-labeled HuM195 (1 mCi/kg)		Bismuth-labeled HuM195 (1.25 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bismuth-labeled HuM195 (0.5 mCi/kg)		Bismuth-labeled HuM195 (0.75 mCi/kg)		Bismuth-labeled HuM195 (1 mCi/kg)		Bismuth-labeled HuM195 (1.25 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/3 (66.7%)		3/20 (15%)		3/6 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	2/3 (66.7%)	2	2/3 (66.7%)	2	0/20 (0%)	0	1/6 (16.7%)	1
Infections and infestations
Infection	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	0/6 (0%)	0
Investigations
Bilirubin increased	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	0/6 (0%)	0
Nervous system disorders
Syncope	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/3 (0%)	0	0/3 (0%)	0	0/20 (0%)	0	1/6 (16.7%)	1
Pneumonitis	0/3 (0%)	0	0/3 (0%)	0	0/20 (0%)	0	1/6 (16.7%)	1
Respiratory disorder	0/3 (0%)	0	0/3 (0%)	0	0/20 (0%)	0	2/6 (33.3%)	2
Other (Not Including Serious) Adverse Events
	Bismuth-labeled HuM195 (0.5 mCi/kg)		Bismuth-labeled HuM195 (0.75 mCi/kg)		Bismuth-labeled HuM195 (1 mCi/kg)		Bismuth-labeled HuM195 (1.25 mCi/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		17/20 (85%)		6/6 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	1/3 (33.3%)	1	2/3 (66.7%)	3	1/20 (5%)	1	2/6 (33.3%)	2
Anemia	2/3 (66.7%)	2	1/3 (33.3%)	2	10/20 (50%)	58	2/6 (33.3%)	5
Cardiac disorders
Sinus tachycardia	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	1/6 (16.7%)	1
Gastrointestinal disorders
Nausea	0/3 (0%)	0	0/3 (0%)	0	2/20 (10%)	2	3/6 (50%)	4
General disorders
Fatigue	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	1/6 (16.7%)	1
Fever	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	1	2/6 (33.3%)	2
Hemorrhage, other	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	2	1/6 (16.7%)	1
Rigors, chills	0/3 (0%)	0	0/3 (0%)	0	4/20 (20%)	4	0/6 (0%)	0
Immune system disorders
Allergic Reaction	0/3 (0%)	0	0/3 (0%)	0	4/20 (20%)	4	0/6 (0%)	0
Infections and infestations
Infection, other	1/3 (33.3%)	1	3/3 (100%)	5	14/20 (70%)	28	3/6 (50%)	6
Investigations
Creatinine increased	1/3 (33.3%)	2	0/3 (0%)	0	4/20 (20%)	7	1/6 (16.7%)	1
White blood cell decreased	2/3 (66.7%)	8	3/3 (100%)	6	15/20 (75%)	106	6/6 (100%)	46
Neutrophil count decreased	1/3 (33.3%)	2	2/3 (66.7%)	9	7/20 (35%)	18	4/6 (66.7%)	13
Platelet count decreased	0/3 (0%)	0	2/3 (66.7%)	15	12/20 (60%)	83	4/6 (66.7%)	36
Alkaline phosphatase increase	0/3 (0%)	0	0/3 (0%)	0	4/20 (20%)	6	0/6 (0%)	0
Blood bilirubin increase	0/3 (0%)	0	0/3 (0%)	0	7/20 (35%)	34	3/6 (50%)	5
Aspartate aminotransferase increase	0/3 (0%)	0	0/3 (0%)	0	2/20 (10%)	3	0/6 (0%)	0
Alanine aminotransferase increase	0/3 (0%)	0	0/3 (0%)	0	6/20 (30%)	13	1/6 (16.7%)	1
Renal and urinary disorders
Hematuria	0/3 (0%)	0	1/3 (33.3%)	1	0/20 (0%)	0	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/3 (0%)	0	1/3 (33.3%)	1	2/20 (10%)	2	2/6 (33.3%)	4
Dyspnea	0/3 (0%)	0	0/3 (0%)	0	2/20 (10%)	2	2/6 (33.3%)	2
Hypoxia	0/3 (0%)	0	0/3 (0%)	0	1/20 (5%)	2	3/6 (50%)	3
Adult Respiratory Distress Syndrome	0/3 (0%)	0	0/3 (0%)	0	0/20 (0%)	0	2/6 (33.3%)	2
Skin and subcutaneous tissue disorders
Derm, skin other	1/3 (33.3%)	1	0/3 (0%)	0	2/20 (10%)	2	0/6 (0%)	0
Vascular disorders
Hypotension	0/3 (0%)	0	0/3 (0%)	0	2/20 (10%)	2	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

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.