Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01181258
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 71
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

In this study the investigators investigate a cell therapy strategy that could harness allogeneic effectors that can potentially mediate anti-lymphoma effect. The investigators have designed a novel lymphodepleting conditioning regimen followed by infusion of donor-derived natural killer (NK) cells and interleukin-2 (IL-2) for patients with refractory lymphoid malignancies.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia	Drug: Rituximab; Biological: Interleukin-2; Biological: Natural killer cells; Drug: Cyclophosphamide; Drug: Methylprednisolone; Drug: Fludarabine	Phase 2

Detailed Description

This is a single center phase II trial designated to expand donor NK cells and induce remissions in patients with refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) using chemotherapy followed by haploidentical NK cells and IL2.

Primary Objective is to evaluate the objective response rate (PR+CR) at 2 months post haploidentical NK cell infusion in patients with refractory Non Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Secondary Objective is to 1) evaluate the safety and tolerability of lymphodepleting chemotherapy, rituximab, and methylprednisone as determined by incidence of serious adverse events; 2) evaluate in vivo expansion of allogeneic donor NK cells at day 14; 3) determine time to progression

Exploratory Objective is to 1) correlate clinical response with frequencies of peripheral blood T reg cells after chemotherapy; 2) correlate clinical response with donor KIR-B-content score determined by genotype; 3) monitor phenotypic and functional characteristics of natural killer cells and regulatory T cells in vivo; 4) correlate clinical response with donor FcR polymorphism.

• Pre-NK cell infusion chemotherapeutic regimen consist of 1) Rituximab 375mg/m2 IV weekly x 4, start day -7; 2) Fludarabine 25 mg/m2 IV day -6 through day -2; 3) Cyclophosphamide 60mg/kg IV day -5; 4) Methylprednisolone 1 mg/kg day -2 through day +9.

• NK cell infusion using IL2 activated donor NK cells 1.5 to 8 x 107 cells/kg IV day 0

• IL2 SC 9 million IU every other day x 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule

Accrual Goal: Up to 17 patients will be enrolled

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Patients Receiving NK Cell Infusion Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL

Drug: Rituximab; 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK); Other Names: Rituxan MabThera ; Biological: Interleukin-2; subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule.; Other Names: IL-2 ; Biological: Natural killer cells; administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion); Other Names: NK cells ; Drug: Cyclophosphamide; 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine.; Other Names: Cytoxan ; Drug: Methylprednisolone; 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion.; Other Names: Medrol ; Drug: Fludarabine; 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through day -2).; Other Names: Fludara

Outcome Measures

Primary Outcome Measures

1. Number of Patients With an Objective Response [Month 2 Post Infusion]

   The number of patients with a partial response (PR) or complete response (CR). For patients with non-hodgkin's lymphoma: CR - complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR - at least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. For patients with chronic lymphocytic leukemia: CR - disappearance of all palpable disease, normalization of the blood counts without transfusions, bone marrow aspirate lymphocyte percentage < 30%, and no evidence of disease on bone marrow biopsy. PR - 50% or more reduction in palpable disease as well as one or more of the remaining features: neutrophils >= 1.5 × 109/L or 50% improvement over baseline, platelets more than 100 × 109/L or 50% improvement over baseline, and hemoglobin more than 11.0 g/dL or 50% improvement over baseline without transfusions.

Secondary Outcome Measures

1. Serious Adverse Events [Day 1 through Month 12]

   Number of participants experiencing serious adverse events that occur during study. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL2 injections.

2. Time to Disease Progression [Day 1 through Month 12]

   Cumulative incidence will be used to determine time to disease progression.

3. Patients With Expansion of NK Cells [Day 14]

   Number of patients who experience in vivo expansion of allogeneic donor natural killer (NK) cells.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients of any age with diagnosis of:

• Relapsed/refractory lymphoma (B cell non-Hodgkin) who have lack of objective response to at least two prior chemotherapy regimens

• Relapsed chronic lymphocytic leukemia with high risk features: lack of objective response or relapse within 6 months following nucleoside-analogue based chemotherapy regimen or patients with 17p deletion CLL who lacked objective response to at least 1 preceding chemotherapy regimen

• Available related HLA haploidentical NK cell donor by at least Class I serologic typing at the A&B locus (age 12-75 years)

• Karnofsky > 70% for patients 16 years and older and Lansky play score > 50 for patients under 16 years of age

• Measurable disease based on modified Response Evaluation Criteria in Solid Tumors (RECIST)

• Have acceptable organ function as defined within 28 days of enrollment:

• Hematologic: platelets ≥ 80,000 x 10^{9/L; hemoglobin ≥ 9 g/dL, unsupported by transfusions within 7 days; absolute neutrophile count (ANC) ≥ 1000 x 10}9/L, unsupported by Granulocyte colony-stimulating factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) for 10 days or Neulasta for 21 days - the hematologic requirements are waived for patients with inadequate counts due to known bone marrow involvement by disease who are otherwise eligible

• Renal: calculated glomerular filtration rate (GFR) > 50 ml/min

• Hepatic: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 x upper limit of normal and total bilirubin ≤3 mg/dl - hepatic requirements are waived for patients with known disease involvement in the liver if otherwise eligible

• Pulmonary function: >40% corrected Carbon Monoxide Diffusing Capacity (DLCO) and Forced expiratory volume in one second (FEV1) (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)

• Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection fraction ≥ 40%

• Able to be off prednisone or other immunosuppressive medications for at least 3 day prior to Day 0 (excluding denileukin diftitox pre-medications)

• Sexually active women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.

• Voluntary written consent

Exclusion Criteria:

• Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 14 days prior to enrollment to rule out pregnancy. Women of childbearing age must use appropriate contraceptive method.

• Active central nervous system (CNS) lymphoma/leukemia - Patients with prior CNS involvement are eligible provided that it has been treated and is in remission.

• Active serious infection (pulmonary infiltrates or lesions are allowed only after the appropriate diagnostic testing is negative for infection or appropriate therapy was initiated for probable infection)

• Pleural effusion large enough to be detectable on chest x-ray (CXR)

• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology

• Active concurrent malignancy (except skin cancer)

• Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder

• Positive HBsAg. If HBcAb is positive, Hepatitis B DNA by PCR will be evaluated. Positive anti HBcAb with an undetectable viral load does not exclude the patient.

• Any investigational therapy in the past 30 days

• Patients following allogeneic stem cell transplantation are eligible in the absence of graft versus host disease and are off immunosuppression for at least 30 days

• Known allergy to any of the study agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Veronika Bachanova, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT01181258
• Other Study ID Numbers: 2009LS083; MT2009-15; 1002M77545
• First Posted: Aug 13, 2010
• Last Update Posted: Feb 6, 2018
• Last Verified: Jan 1, 2016

• Keywords provided by Masonic Cancer Center, University of Minnesota: related HLA-haploidentical donor
• Additional relevant MeSH terms: Leukemia, Lymphocytic, Chronic, B-Cell; Methylprednisolone; Cyclophosphamide; Rituximab; Fludarabine; Interleukin-2

Study Results

Participant Flow

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 87.5%
>=65 years	2 12.5%
Sex: Female, Male (Count of Participants)
Female	3 18.8%
Male	13 81.3%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With an Objective Response
Description	The number of patients with a partial response (PR) or complete response (CR). For patients with non-hodgkin's lymphoma: CR - complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR - at least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. For patients with chronic lymphocytic leukemia: CR - disappearance of all palpable disease, normalization of the blood counts without transfusions, bone marrow aspirate lymphocyte percentage < 30%, and no evidence of disease on bone marrow biopsy. PR - 50% or more reduction in palpable disease as well as one or more of the remaining features: neutrophils >= 1.5 × 109/L or 50% improvement over baseline, platelets more than 100 × 109/L or 50% improvement over baseline, and hemoglobin more than 11.0 g/dL or 50% improvement over baseline without transfusions.
Time Frame	Month 2 Post Infusion

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable. One patient died prior to receiving NK cell infusion and one did not survive by day 14; therefore 14 patients were analyzed for this outcome measure.

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Measure Participants	14
Count of Participants [Participants]	4 25%

2. Secondary Outcome

Title	Serious Adverse Events
Description	Number of participants experiencing serious adverse events that occur during study. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL2 injections.
Time Frame	Day 1 through Month 12

Outcome Measure Data

Analysis Population Description

One participant developed sepsis prior to receiving the NK cell infusion and was withdrawn from the study.

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Measure Participants	15
Count of Participants [Participants]	15 93.8%

3. Secondary Outcome

Title	Time to Disease Progression
Description	Cumulative incidence will be used to determine time to disease progression.
Time Frame	Day 1 through Month 12

Outcome Measure Data

Analysis Population Description

10 participants had disease progression

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Measure Participants	10
Median (Full Range) [days]	38

4. Secondary Outcome

Title	Patients With Expansion of NK Cells
Description	Number of patients who experience in vivo expansion of allogeneic donor natural killer (NK) cells.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable. One patient died prior to receiving NK cell infusion and one did not survive by day 14; therefore 14 patients were analyzed for this outcome measure.

Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
Measure Participants	14
Count of Participants [Participants]	0 0%

Adverse Events

Adverse Event Reporting Description	Fifteen patients were dosed with the NK cell infusion and therefore were assessed for adverse events. One patient died prior to the NK cell infusion.
Arm/Group Title	Patients Receiving NK Cell Infusion
Arm/Group Description	Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab: 375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) Interleukin-2: subcutaneously administered 9 million international units (IU) every other day * 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same schedule. Natural killer cells: administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion) Cyclophosphamide: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine Methylprednisolone: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion Fludarabine: 25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through
All Cause Mortality
	Patients Receiving NK Cell Infusion
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients Receiving NK Cell Infusion
	Affected / at Risk (%)	# Events
Total	6/15 (40%)
Blood and lymphatic system disorders
Thrombotic Thrombocytopenic Purpura	1/15 (6.7%)
Febrile Neutropenia	2/15 (13.3%)
Cardiac disorders
Hypertension	1/15 (6.7%)
Infections and infestations
Sepsis	2/15 (13.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/15 (6.7%)
Bronchospasm	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Patients Receiving NK Cell Infusion
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Neutropenic Fever	8/15 (53.3%)
Cardiac disorders
Prolonged QTC Interval	1/15 (6.7%)
Tachycardia	2/15 (13.3%)
Eye disorders
Chemosis, Eye	1/15 (6.7%)
Dry Eyes	1/15 (6.7%)
Gastrointestinal disorders
Nausea	1/15 (6.7%)
General disorders
Chest Pain	1/15 (6.7%)
Chills	14/15 (93.3%)
Edema	8/15 (53.3%)
Fever	9/15 (60%)
Flu-like Symptoms	1/15 (6.7%)
Infusion Related Reaction	6/15 (40%)
Injection Site Reaction	8/15 (53.3%)
Tumor Pain	1/15 (6.7%)
Upper Extremity Swelling/Edema	2/15 (13.3%)
Investigations
Creatinine Increased	3/15 (20%)
Weight Gain	2/15 (13.3%)
Metabolism and nutrition disorders
Tumor Lysis Syndrome	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Back/Chest Spasms	1/15 (6.7%)
Left Jaw Pain	1/15 (6.7%)
Leg Pain	1/15 (6.7%)
Neck Pain	1/15 (6.7%)
Nervous system disorders
Headache	6/15 (40%)
Peripheral Neuropathy	1/15 (6.7%)
Psychiatric disorders
Confusion	1/15 (6.7%)
Renal and urinary disorders
Acute Kidney Injury	2/15 (13.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/15 (33.3%)
Hypoxia	3/15 (20%)
Nasal Congestion	1/15 (6.7%)
Pneumonitis/Pulmonary Infiltrates	3/15 (20%)
Skin and subcutaneous tissue disorders
Rash/Desquamation	7/15 (46.7%)
Vascular disorders
Capillary Leak Syndrome	1/15 (6.7%)
Hypertension	14/15 (93.3%)
Hypotension	8/15 (53.3%)

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.