Trial of the Histone-Deacetylase Inhibitor ITF2357 Followed by Mechlorethamine in Relapsed/Refractory Hodgkin's Lymphoma

• Sponsor: Italfarmaco (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00792467
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study has the following objectives:

Primary Objective

• To evaluate the anti-lymphoma efficacy of daily oral doses of ITF2357 followed by intravenous Mechlorethamine administered to patients with refractory/relapsed Hodgkin's lymphoma.

Secondary Objective

• To evaluate the safety and tolerability of multiple courses of ITF2357 followed by Mechlorethamine in a population of chemotherapy pretreated patients.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Lymphoma	Drug: ITF2357	Phase 1/Phase 2

Detailed Description

This is a single-center, open label, phase II study aimed at testing the activity of multiple cycles of ITF2357 followed by Mechlorethamine administered to patients with relapsed/refractory Hodgkin's lymphoma.

Patients will receive a maximum of twelve 3-week cycles of ITF2357 followed by

Mechlorethamine according to the following schema:

• ITF2357, 50 mg every 6 hours, per os, days 1 - 3

• Mechlorethamine, 6 mg/sqm, intravenously , day 4 Study therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable adverse events or patient's request to discontinue treatment occurs, but in any case for a maximum of 12 cycles.

Decision regarding the continuation of ITF2357/Mechlorethamine therapy will be made on (i)the basis of tumor reassessment following cycles 2, 6, 9, and 12 and (ii) the occurrence of toxicity. Tumor response will be evaluated according to the International Working Group response criteria HL.

Treatment will be administrated on an outpatient basis and patients will be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalisation, the treatment will be continued or interrupted according to the Investigators' decision.

The study will accrue 23 patients evaluable for efficacy and the anticipated duration of the study is about 24 months.

Histone deacetylases (HDACs) are enzymes involved in the remodeling of chromatin, and have a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypoacetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies.

Hodgkin's lymphoma (HL) is a relatively uncommon lymphoma histotype, with an incidence in Italy of approximately 1700 new cases per year (approximately 12% of all lymphomas). Combination chemotherapy with or without radiotherapy cures approximately 70 percent of advanced-stage HL. Fifty percent of the failing patients can be salvaged by second line chemotherapy (mainly high-dose regimens), while the remaining patients eventually die by disease progression. The development of an effective salvage regimen for this refractory/resistant population represents a true unmet medical need.

The use in the latter patient subset of HDAC inhibitors, like ITF2357, is supported by several considerations. Namely: (1) a related hydroxamate, SAHA, has shown activity in this clinical condition; (2) the drug markedly inhibits the production of several cytokines, and cytokine production in HL granuloma has a defined role in the pathogenesis of HL; (3) an effective treatment for refractory/relapsed HL is presently lacking; (4) ITF2357, up to 200 mg daily per os, has shown a favorable toxicity profile. All the above mentioned arguments represent a strong rationale prompting the use of ITF2357 in this patient population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of the Histone-Deacetylase Inhibitor ITF2357 Followed by Mechlorethamine in Relapsed/Refractory Hodgkin's Lymphoma Patients
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ITF2357 Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there was no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. The mean number of complete treatment cycles received by patients was 5.25, with a minimum of 1 cycle and a maximum of 12 cycles.

Drug: ITF2357; ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.; Other Names: Givinostat, histone deacetylase inhibitor

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [At each 21-day cycle for a maximum of 12 cycles]

   OR rate among patients treated is defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. In medicine, a response rate is the percentage of patients whose cancer shrinks or disappears after treatment. The FDA definition of ORR is the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.

2. Proportion of Responders (Complete -CR- or Partial PR-) [At each 21-day cycle for a maximum of 12 cycles]

   Complete responder (CR) and partial responder (PR) among patients treated are defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is defined as regression of measurable disease and no new sites. The frequencies of patients achieving objective response (i.e. subjects whose best overall response was CR or PR) and the frequencies of patients who did not achieve an objective response (i.e.subjects whose best overall response was equal to stable disease - SD, progressive disease - PD - or not evaluable) in ITT and PP populations are reported. NED= no evidence of disease

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, assessed up to 450 days from the start of the first cycle of treatment]

   PFS is defined as the time from the 1st day of the 1st cycle of treatment until objective tumor progression or death. It included deaths, thus could be correlated to overall survival. If a patient did not have disease progression, PFS was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).

2. Time To Response (TTR) [From the first day of the first cycle until the date of achieving a response assessed up to 250 days from the start of the first cycle of treatment]

   TTR is defined as the time from the 1st day of the 1st cycle until the date of achieving a response (CR or PR). In case of no objective response, TTR was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).

3. Response Duration (RD): [From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, or last available tumor assessment (assessed up to 350 days from the start of the first cycle of treatment).]

   Duration of objective response (CR or PR) was applied only to patients whose best overall response was CR or PR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Written Informed Consent;

• Age ≥18 years;

• Histologically confirmed diagnosis of Hodgkin's lymphoma;

• Subjects who have failed second-line or subsequent-line salvage chemo- radiotherapy regimens for whom no other treatment options of proven efficacy can be given;

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements;

• ANC ≥1500/µL; Platelet count ≥75000/µL;

• Hemoglobin ≥9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level);

• Total bilirubin ≤1.6 mg/dL; AST or ALT ≤2.5 times the upper limit of normal;

• Serum creatinine ≤2.0 mg/dL or creatinine clearance >50 mL/min;

• Serum Potassium and Magnesium within normal limits;

• Subjects with at least one bi-dimensional lesion measurable by CT-scan or MRI, according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group (J Clin Oncol, 25:579-586, 2007);

• ECOG performance status of 0 or 1;

• Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential;

• Life expectancy of >3 months;

• Subjects receiving intravenous Mechlorethamine (6 mg/sqm) as single agent at least 4 weeks before study entry;

• Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

• Active bacterial or mycotic infection requiring antimicrobial treatment

• Pregnancy or lactation

• Anticancer chemotherapy or radiotherapy during the study or within 4 weeks of study entry.

• A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula - see appendix I for the formula)

• Use of concomitant medications that prolong the QT/QTc interval (see appendix H for full list)

• Clinically significant cardiovascular disease including:

• Uncontrolled hypertension, myocardial infarction, unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of any cardiac arrhythmia requiring medication (irrespective of its severity)

• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

• Positive blood test for HIV, HBV and HCV

• Identification of viral DNA by quantitative PCR for EBV and JC virus.

• History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Istituto Nazionale per la Cura e lo Studio dei Tumori	Milano		Italy	20133

Sponsors and Collaborators

• Italfarmaco

Investigators

• Principal Investigator: Alessandro Massimo Gianni, MD, Istituto Nazionale per la Cura e lo Studio dei Tumori, Milano, Italy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Italfarmaco
• ClinicalTrials.gov Identifier: NCT00792467
• Other Study ID Numbers: DSC/07/2357/31; 2007-007091-41
• First Posted: Nov 18, 2008
• Last Update Posted: May 11, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Histone Deacetylase Inhibitors; Givinostat hydrochloride

Study Results

Participant Flow

Recruitment Details	Patients enrolled were 24 subjects of both genders, age ≥18 years, with histologically confirmed diagnosis of Hodgkin's lymphoma and refractory or relapsed.

Arm/Group Title	ITF2357
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Period Title: Overall Study
STARTED	24
COMPLETED	2
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	ITF2357
Arm/Group Description	Patients will receive the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.83 (14.49)
Sex: Female, Male (Count of Participants)
Female	5 20.8%
Male	19 79.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 95.8%
Not Hispanic or Latino	1 4.2%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Italy	24 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	OR rate among patients treated is defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. In medicine, a response rate is the percentage of patients whose cancer shrinks or disappears after treatment. The FDA definition of ORR is the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.
Time Frame	At each 21-day cycle for a maximum of 12 cycles

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.

Arm/Group Title	ITT Population	PP Population
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Measure Participants	24	16
Objective Response achieved	25.00	37.50
Objective Response not achieved	75.00	62.50

2. Primary Outcome

Title	Proportion of Responders (Complete -CR- or Partial PR-)
Description	Complete responder (CR) and partial responder (PR) among patients treated are defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is defined as regression of measurable disease and no new sites. The frequencies of patients achieving objective response (i.e. subjects whose best overall response was CR or PR) and the frequencies of patients who did not achieve an objective response (i.e.subjects whose best overall response was equal to stable disease - SD, progressive disease - PD - or not evaluable) in ITT and PP populations are reported. NED= no evidence of disease
Time Frame	At each 21-day cycle for a maximum of 12 cycles

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.

Arm/Group Title	ITT Population	PP Population
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Measure Participants	24	16
CR/NED	4.17 17.4%	6.25 NaN
PR	20.83 86.8%	31.25 NaN
SD	29.17 121.5%	25.00 NaN
PD	37.50 156.3%	37.50 NaN
Not evaluable	8.33 34.7%	0 NaN

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from the 1st day of the 1st cycle of treatment until objective tumor progression or death. It included deaths, thus could be correlated to overall survival. If a patient did not have disease progression, PFS was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).
Time Frame	From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, assessed up to 450 days from the start of the first cycle of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.

Arm/Group Title	ITT Population	PP Population
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Measure Participants	24	16
Mean (Standard Deviation) [Days]	164.53 (28.66)	183.94 (39.38)

4. Secondary Outcome

Title	Time To Response (TTR)
Description	TTR is defined as the time from the 1st day of the 1st cycle until the date of achieving a response (CR or PR). In case of no objective response, TTR was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).
Time Frame	From the first day of the first cycle until the date of achieving a response assessed up to 250 days from the start of the first cycle of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.

Arm/Group Title	ITT Population	PP Population
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Measure Participants	24	16
Mean (Standard Deviation) [Days]	123.52 (11.70)	114.34 (14.81)

5. Secondary Outcome

Title	Response Duration (RD):
Description	Duration of objective response (CR or PR) was applied only to patients whose best overall response was CR or PR.
Time Frame	From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, or last available tumor assessment (assessed up to 350 days from the start of the first cycle of treatment).

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.

Arm/Group Title	ITT Population	PP Population
Arm/Group Description	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.	Patients received the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
Measure Participants	6	6
Mean (Standard Deviation) [Days]	199.96 (42.77)	199.96 (42.77)

Adverse Events

Time Frame	Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
Arm/Group Title	ITF2357
Arm/Group Description	Patients will receive the following therapy cycle ITF2357, 50 mg every 6 hours, per os, days 1 - 3; Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
All Cause Mortality
	ITF2357
	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)
Serious Adverse Events
	ITF2357
	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/24 (4.2%)	1
Dyspnoea	1/24 (4.2%)	1
Fever	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	ITF2357
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Blood and lymphatic system disorders
Anaemia	12/24 (50%)
Febrile neutropenia	1/24 (4.2%)
Cardiac disorders
Leukopenia	1/24 (4.2%)
Neutropenia	11/24 (45.8%)
Thrombocytopenia	16/24 (66.7%)
Atrial fibrillation	1/24 (4.2%)
Gastrointestinal disorders
Abdominal pain	2/24 (8.3%)
Diarrhoea	5/24 (20.8%)
Dysphagia	1/24 (4.2%)
Haemorrhoidal haemorrhage	1/24 (4.2%)
Nausea	7/24 (29.2%)
Stomatitis	1/24 (4.2%)
Vomiting	5/24 (20.8%)
General disorders
Asthenia	6/24 (25%)
chest pain	1/24 (4.2%)
Extravasation	1/24 (4.2%)
Fatigue	1/24 (4.2%)
Injection site reaction	1/24 (4.2%)
Pyrexia	7/24 (29.2%)
Immune system disorders
Graft versus host disease	1/24 (4.2%)
Infections and infestations
Infection	2/24 (8.3%)
Skin infection	1/24 (4.2%)
Upper respiratory tract infection	3/24 (12.5%)
Investigations
Alanine aminotransferase increased	1/24 (4.2%)
Aspartate aminotransferase increased	1/24 (4.2%)
Platelet count decreased	1/24 (4.2%)
Metabolism and nutrition disorders
Anorexia	2/24 (8.3%)
Hypokalaemia	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Bone pain	1/24 (4.2%)
Musculoskeletal pain	1/24 (4.2%)
Nervous system disorders
Headache	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	6/24 (25%)
Dyspnoea	5/24 (20.8%)
Epistaxis	1/24 (4.2%)
Oropharyngeal pain	3/24 (12.5%)
Pharyngeal inflammation	1/24 (4.2%)
Pneumonitis	3/24 (12.5%)
Skin and subcutaneous tissue disorders
Butterfly rash	1/24 (4.2%)
Hyperhidrosis	1/24 (4.2%)
Pruritus	1/24 (4.2%)
Rash	2/24 (8.3%)
Vascular disorders
Deep vein thrombosis	1/24 (4.2%)

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.