Pasireotide in Prevention of GI Toxicity

• Sponsor: Anthony Sung, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT02215070
• Collaborator: Massachusetts General Hospital (Other)
• Enrollment: 37
• Locations: 2
• Arm: 1
• Actual Duration (Months): 56.8
• Patients Per Site: 18.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic stem cell transplant. The study will also evaluate if Pasireotide is effective in reducing acute and chronic Graft-versus-Host-Disease (GvHD) after transplant.

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancies	Drug: Pasireotide	Phase 2

Detailed Description

The study design will be a non-randomized phase II. Forty patients receiving an ablative preparatory regimen will receive pasireotide subcutaneous (0.9 mg, b.i.d.) one day prior to initiation of the preparatory regimen and continuing for eight days following the completion of the preparatory regimen not to exceed 14 days total dosing. We select matched controls from existing patients who did not take the drug to minimize the time it takes to complete the trial.

Myeloablative preparatory regimens are defined as those including either TBI ≥ 1200 cGy or busulfan ≥ 12.8 mg/kg. The most common regimens combine TBI with cyclophosphamide (TBI/Cy) or busulfan with cyclophosphamide (Bu/Cy) (Appendix E). However, any regimen meeting the above definition of myeloablative preparatory regimen may be used.

The study will collect data at screening, at baseline prior to initiation of the drug (day of study drug start), transplant day 0, day +7, day +14 and weekly thereafter until day +100, and on days +180, +270, and +365. The total days on pasireotide therapy will be recorded as well as any SAE that is outside the expected for stem cell transplantation. We will also follow the incidence and severity of acute and chronic GVHD.

At Duke only, a video capsule endoscopy will be performed in a subset of ten study patients between transplant days +4 through +6. This substudy is descriptive in nature and only used to collect a source of preliminary data that may suggest further study.

Patients must agree to participate in this portion of the study and will be asked to sign a clinical consent for performance use of the video capsule endoscopy. Patients will be given detailed instructions to prepare for the procedure. An investigator who is blinded to the group allocation of the patients/volunteers separately will review the images obtained from each of the capsule examinations. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis. Each of these categories will be scored from 0-3 and summed to obtain an overall index that will range from 0 (normal study) to 12 (severely abnormal in all categories).

Citrulline assay Measurement of citrulline concentration has been used as a marker for cytotoxic treatment-induced intestinal damage and it is highly reproducible. The citrulline concentration appears to be a quantitative parameter that is independent of the underlying cause for epithelial cell loss and functions well in the post-SCT setting. Six mls of blood will be collected in heparinized tubes on days 0, 7, and 14. Tubes will be centrifuged according to manufacturer's instructions and the plasma will be collected and stored at -80C until shipment to the laboratory performing the assay.

Calprotectin assay Calprotectin has been described as another biomarker of GI injury. During radiation-induced inflammation, leucocytes infiltrate the mucosa and increase the level of fecal calprotectin. At least 50 mg of stool specimen will be collected from patients on days 0, 7, and 14. Samples will be stored at -80C until shipment to the laboratory performing the assay. Calprotectin will be measured with an ELISA kit (CALPRO, Oslo, Norway) in accordance with the manufacturer's instructions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prevention of Gastrointestinal Toxicity From Total Body Irradiation or High Dose Chemotherapy With Pasireotide
• Actual Study Start Date: Jan 21, 2015
• Actual Primary Completion Date: Feb 28, 2019
• Actual Study Completion Date: Oct 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pasireotide + Preparatory Regimen Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Drug: Pasireotide; Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.

Outcome Measures

Primary Outcome Measures

1. Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide [30 Days]

   Number of participants who experience grades III-IV GI toxicity

Secondary Outcome Measures

1. Percentage of Acute GVHD [100 days]

   Number of participants who experience acute GVHD

2. Maximum Severity of Acute GVHD Compared to Historical Controls [100 days]

   Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards

3. Incidence of Chronic GVHD Compared to Historical Controls [1 year]

   Measure the number of participants who experience chronic GVHD

4. Maximum Severity of Chronic GVHD Compared to Historical Controls [1 year]

   Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria

5. Overall Survival Compared to Historical Controls [1 year]

   Rate of overall survival of participants at one year post transplant

6. Disease Free Survival Compared to Historical Controls [1 year]

   Rate of disease free survival of participants at one year post transplant

Other Outcome Measures

1. Citrulline and Fecal Calprotectin Levels Will be Measured [100 days]

   Exploratory outcome-These levels will be evaluated as biomarkers of GI tract health and function in SCT patients and the correlation between these biomarkers and GI toxicity.

2. Evaluate GI Toxicity Assessment by Video Capsule Endoscopy. [14 days]

   Exploratory outcome-Video capsule endoscopy will be performed in a subset of ten study participants on the last day study drug is administered. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older at the time of study enrollment.

• Histologically confirmed diagnosis for which an allogeneic transplant is utilized.

• Plan to receive an allogeneic transplant from a 4-6/6 single or dual umbilical cord blood graft, or a 7-8/8 HLA-matched sibling or unrelated donor (High resolution HLA-A, B, C, DRB1).

• Meet standard criteria as defined by the institution for a myeloablative allogeneic stem cell transplantation, with myeloablative defined as using conditioning regimens containing:

• TBI ≥ 1200 cGy, or

• Busulfan ≥ 12.8mg/kg

• Patient must have given written informed consent according to FDA guidelines.

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

• Female patients who are pregnant or lactating, or are of childbearing potential (FCBP, defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control

• FCBP must have a current negative serum pregnancy test prior to transplant per institutional practice.

• Use of an investigational drug within 1 month prior to dosing. Concurrent enrollment on other clinical research studies that contain an interventional therapy is not permitted while subjects are receiving pasireotide or within 5 half-lives of finishing pasireotide. However, subjects may concurrently enroll in non-interventional studies (e.g. biobanking, mobile health tracking).

• Active CNS disease (related to primary malignancy) at the time of enrollment.

• Patients with existing grade 2 toxicities, except as approved by the investigator.

• Any of the following diseases or conditions:

Cardiac:

• History of unexplained syncope or family history of idiopathic sudden death.

• Sustained or clinically significant cardiac arrhythmias.

• Risk factors for Torsades de Pointes such as:

• Uncontrolled hypokalemia

• Uncontrolled hypomagnesemia or hypermagnesemia

• Cardiac failure (New York Heart Association Class II or higher)

• Clinically significant/symptomatic bradycardia (HR < 50), or high-grade AV block.

• Known diagnosis of QT prolongation (QTc ≥ 470) or family history of long QT syndrome

• Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure.

• Concomitant medications known to prolong the QT interval during the same time as pasireotide is to be administered (unless approved by PI and QTc < 470; standard transplant medications that are known to prolong the QT (e.g. azoles, ondansetron, etc.) are permitted but caution is advised and patients should be closely monitored).

Endocrine:

• Uncontrolled diabetes at the time of cytoreduction. All patients with diabetes must be optimized on their diabetes regimen prior to initiating pasireotide.

• If a patient is diabetic: uncontrolled diabetes as defined by HbA1c > 8 per cent despite adequate therapy

• Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months.

• Known diagnosis of hypocortisolism

• Known diagnosis of pituitary hormone deficiency.

• Known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR or s.c. formulations.

Infectious:

• Uncontrolled (not being treated) infections at the time of cytoreduction.

• A positive HIV test result (ELISA and Western blot) or history of known HIV. An HIV test will not be required; however, previous medical history will be reviewed.

Gastrointestinal:

• Moderately impaired hepatic function (Child-Pugh B) or severe hepatic impairment (Child-Pugh C)

• Known gallbladder or bile duct disease, symptomatic cholelithiasis, acute or chronic pancreatitis.

• Known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.

Hematologic:

• Abnormal coagulation (PT or aPTT > 30% above normal limits).

• Continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.

Miscellaneous:

• Major surgery/surgical therapy for any cause within 1 month prior to pasireotide administration. Patients should have recovered and have a good clinical condition before entering the study.

• Any co-morbid condition which, in the view of the Principal Investigator, renders the patient at high risk from treatment complications.

Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Duke University Medical Center	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Anthony Sung, MD
• Massachusetts General Hospital

Investigators

• Principal Investigator: Anthony Sung, MD, Duke University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 20, 2017

More Information

Publications

None provided.

• Responsible Party: Anthony Sung, MD, Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT02215070
• Other Study ID Numbers: Pro00051736
• First Posted: Aug 13, 2014
• Last Update Posted: Nov 17, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Anthony Sung, MD, Professor of Medicine, Duke University: Allogeneic Stem Cell Transplantation; Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Acute Non-Lymphocytic Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia; Lymphoma
• Additional relevant MeSH terms: Hematologic Neoplasms; Pasireotide

Study Results

Participant Flow

Pre-assignment Detail	5 enrolled participants screen failed, 5 withdrew, and 1 was withdrawn by physician decision.

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
Period Title: Overall Study
STARTED	26	52
COMPLETED	20	52
NOT COMPLETED	6	0

Baseline Characteristics

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls	Total
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).	Total of all reporting groups
Overall Participants	26	52	78
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58	51	52
Sex: Female, Male (Count of Participants)
Female	8 30.8%	23 44.2%	31 39.7%
Male	18 69.2%	29 55.8%	47 60.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 1.9%	1 1.3%
Not Hispanic or Latino	26 100%	46 88.5%	72 92.3%
Unknown or Not Reported	0 0%	5 9.6%	5 6.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.8%	0 0%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.7%	7 13.5%	9 11.5%
White	23 88.5%	43 82.7%	66 84.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 3.8%	2 2.6%
Region of Enrollment (Count of Participants)
United States	26 100%	52 100%	78 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide
Description	Number of participants who experience grades III-IV GI toxicity
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
Measure Participants	26
Count of Participants [Participants]	21 80.8%

2. Secondary Outcome

Title	Percentage of Acute GVHD
Description	Number of participants who experience acute GVHD
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
Measure Participants	26
Count of Participants [Participants]	15 57.7%

3. Secondary Outcome

Title	Maximum Severity of Acute GVHD Compared to Historical Controls
Description	Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
Measure Participants	26
Median (Inter-Quartile Range) [units on a scale]	2

4. Secondary Outcome

Title	Incidence of Chronic GVHD Compared to Historical Controls
Description	Measure the number of participants who experience chronic GVHD
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
Measure Participants	26	52
Count of Participants [Participants]	16 61.5%	22 42.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide + Preparatory Regimen, Historical Controls
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Maximum Severity of Chronic GVHD Compared to Historical Controls
Description	Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
Measure Participants	26	52
Count of Participants [Participants]	8 30.8%	11 21.2%

6. Secondary Outcome

Title	Overall Survival Compared to Historical Controls
Description	Rate of overall survival of participants at one year post transplant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
Measure Participants	26	52
Number (95% Confidence Interval) [percentage of participants]	63 242.3%	82 157.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide + Preparatory Regimen, Historical Controls
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Disease Free Survival Compared to Historical Controls
Description	Rate of disease free survival of participants at one year post transplant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide + Preparatory Regimen	Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.	Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
Measure Participants	26	52
Number (95% Confidence Interval) [percentage of participants]	40 153.8%	78 150%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide + Preparatory Regimen, Historical Controls
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log Rank
	Comments

8. Other Pre-specified Outcome

Title	Citrulline and Fecal Calprotectin Levels Will be Measured
Description	Exploratory outcome-These levels will be evaluated as biomarkers of GI tract health and function in SCT patients and the correlation between these biomarkers and GI toxicity.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Evaluate GI Toxicity Assessment by Video Capsule Endoscopy.
Description	Exploratory outcome-Video capsule endoscopy will be performed in a subset of ten study participants on the last day study drug is administered. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs were reported from the day Pasireotide started to day 30 after transplant (Day +30).
Adverse Event Reporting Description	Adverse event collection is not applicable for historical controls. Adverse events after Day 30 were not expected to be related to the intervention. However, HCT is a fraught process, with significant morbidity, and 10-20% of patients die from transplant-related complications. To determine if the study intervention would improve survival, overall survival was collected at year 1 (efficacy) and adverse events between Day 30-Year 1 were not collected.
Arm/Group Title	Pasireotide + Preparatory Regimen		Historical Controls
Arm/Group Description	Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.		Contemporaneous controls were matched using the following parameters: Transplant diagnosis (acute leukemias, lymphomas, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN]/other), donor (related, unrelated), graft (bone marrow, peripheral blood progenitor cell [PBPC], and cord), GVHD prophylaxis (tacrolimus/methotrexate), age, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning regimen (TBI-based, chemotherapy only).
All Cause Mortality
	Pasireotide + Preparatory Regimen		Historical Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		0/0 (NaN)
Serious Adverse Events
	Pasireotide + Preparatory Regimen		Historical Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/26 (30.8%)		0/0 (NaN)
Cardiac disorders
Mobitz - Type II AV Block	1/26 (3.8%)		1/0 (Infinity)
Gastrointestinal disorders
Enterocolitis	1/26 (3.8%)		1/0 (Infinity)
Hepatobiliary disorders
VOD	1/26 (3.8%)		1/0 (Infinity)
Infections and infestations
Febrile Neutropenia	2/26 (7.7%)		2/0 (Infinity)
Infections and infestations - Other, specify; blood stream	1/26 (3.8%)		1/0 (Infinity)
Lung infection	1/26 (3.8%)		1/0 (Infinity)
Nervous system disorders
Somnolence	1/26 (3.8%)		1/0 (Infinity)
Other (Not Including Serious) Adverse Events
	Pasireotide + Preparatory Regimen		Historical Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		0/0 (NaN)
Blood and lymphatic system disorders
Hematoma	0/26 (0%)		0/0 (NaN)
Thromboembolic event	1/26 (3.8%)		1/0 (Infinity)
Cardiac disorders
Afib	0/26 (0%)		0/0 (NaN)
Sinus Bradycardia	7/26 (26.9%)		7/0 (Infinity)
2nd deg AVB	1/26 (3.8%)		1/0 (Infinity)
Myocardial Infarction	0/26 (0%)		0/0 (NaN)
Pericardial effusion	1/26 (3.8%)		1/0 (Infinity)
Pulmonary Edema	4/26 (15.4%)		4/0 (Infinity)
Endocrine disorders
Hyperglycemia	12/26 (46.2%)		12/0 (Infinity)
Eye disorders
Dry Eyes	2/26 (7.7%)		2/0 (Infinity)
Floaters	0/26 (0%)		0/0 (NaN)
Gastrointestinal disorders
Abdominal Pain	14/26 (53.8%)		14/0 (Infinity)
Anorexia	21/26 (80.8%)		21/0 (Infinity)
Bloating	5/26 (19.2%)		5/0 (Infinity)
Constipation	8/26 (30.8%)		8/0 (Infinity)
Diarrhea	24/26 (92.3%)		24/0 (Infinity)
Dysphagia	1/26 (3.8%)		1/0 (Infinity)
Dyspepsia	5/26 (19.2%)		5/0 (Infinity)
Dysgeusia	9/26 (34.6%)		9/0 (Infinity)
Mucositis	24/26 (92.3%)		24/0 (Infinity)
Ileus	2/26 (7.7%)		2/0 (Infinity)
Nausea	25/26 (96.2%)		25/0 (Infinity)
Vomiting	20/26 (76.9%)		20/0 (Infinity)
Bowel Obstruction	1/26 (3.8%)		1/0 (Infinity)
General disorders
Chills	1/26 (3.8%)		1/0 (Infinity)
Chest pain	2/26 (7.7%)		2/0 (Infinity)
Epistaxis	2/26 (7.7%)		2/0 (Infinity)
Bone Pain	1/26 (3.8%)		1/0 (Infinity)
Dehydration	1/26 (3.8%)		1/0 (Infinity)
Fatigue	20/26 (76.9%)		20/0 (Infinity)
Fracture	1/26 (3.8%)		1/0 (Infinity)
Hiccups	0/26 (0%)		0/0 (NaN)
Insomnia	4/26 (15.4%)		4/0 (Infinity)
Myalgias	0/26 (0%)		0/0 (NaN)
Nasal Congestion	8/26 (30.8%)		8/0 (Infinity)
Pain in Extremity	1/26 (3.8%)		1/0 (Infinity)
Pruritis	2/26 (7.7%)		2/0 (Infinity)
Menorrhagia	0/26 (0%)		0/0 (NaN)
Rhinorrhea	3/26 (11.5%)		3/0 (Infinity)
Toe Trauma	1/26 (3.8%)		1/0 (Infinity)
Hepatobiliary disorders
VOD	1/26 (3.8%)		1/0 (Infinity)
AST Elevation	2/26 (7.7%)		2/0 (Infinity)
ALT Elevation	2/26 (7.7%)		2/0 (Infinity)
Alk Phos Elevation	1/26 (3.8%)		1/0 (Infinity)
Bilirubin Elevation	6/26 (23.1%)		6/0 (Infinity)
Immune system disorders
Allergic reaction	2/26 (7.7%)		2/0 (Infinity)
Infusion Reaction	3/26 (11.5%)		3/0 (Infinity)
Infections and infestations
Enterocolitis	5/26 (19.2%)		5/0 (Infinity)
Febrile Neutropenia	17/26 (65.4%)		17/0 (Infinity)
Fever	4/26 (15.4%)		4/0 (Infinity)
HSV Reactivation	3/26 (11.5%)		3/0 (Infinity)
Lung Infection	4/26 (15.4%)		4/0 (Infinity)
Otitis Media	1/26 (3.8%)		1/0 (Infinity)
Joint Infection	0/26 (0%)		0/0 (NaN)
Skin Infection	3/26 (11.5%)		3/0 (Infinity)
Catheter-Related Infection	6/26 (23.1%)		6/0 (Infinity)
Sinusitis	0/26 (0%)		0/0 (NaN)
Sepsis	7/26 (26.9%)		7/0 (Infinity)
Thrush	4/26 (15.4%)		4/0 (Infinity)
UTI	2/26 (7.7%)		2/0 (Infinity)
Viremia	4/26 (15.4%)		4/0 (Infinity)
Metabolism and nutrition disorders
Hyperkalemia	3/26 (11.5%)		3/0 (Infinity)
Hypernatremia	1/26 (3.8%)		1/0 (Infinity)
Hyponatremia	1/26 (3.8%)		1/0 (Infinity)
Nervous system disorders
Encephalopathy	6/26 (23.1%)		6/0 (Infinity)
Hallucination	3/26 (11.5%)		3/0 (Infinity)
Headache	11/26 (42.3%)		11/0 (Infinity)
Intracranial Hemorrhage	0/26 (0%)		0/0 (NaN)
Peripheral Sensory Neuropathy	2/26 (7.7%)		2/0 (Infinity)
PRES	0/26 (0%)		0/0 (NaN)
Psychiatric disorders
Anxiety	7/26 (26.9%)		7/0 (Infinity)
Renal and urinary disorders
Inreased Creatinine	5/26 (19.2%)		5/0 (Infinity)
Acute Kidney Injury	0/26 (0%)		0/0 (NaN)
Dysuria	6/26 (23.1%)		6/0 (Infinity)
Bladder Spasm	1/26 (3.8%)		1/0 (Infinity)
Hematuria	1/26 (3.8%)		1/0 (Infinity)
Prostatic Obstruction	1/26 (3.8%)		1/0 (Infinity)
Urinary incontinence	1/26 (3.8%)		1/0 (Infinity)
Urinary Retention	3/26 (11.5%)		3/0 (Infinity)
Respiratory, thoracic and mediastinal disorders
Cough	8/26 (30.8%)		8/0 (Infinity)
Dyspnea	7/26 (26.9%)		7/0 (Infinity)
URI	1/26 (3.8%)		1/0 (Infinity)
Hemoptysis	1/26 (3.8%)		1/0 (Infinity)
Hypoxia	7/26 (26.9%)		7/0 (Infinity)
Pleural Effusion	1/26 (3.8%)		1/0 (Infinity)
Pneumonitis	0/26 (0%)		0/0 (NaN)
Skin and subcutaneous tissue disorders
Dry Skin	2/26 (7.7%)		2/0 (Infinity)
Folliculitis	0/26 (0%)		0/0 (NaN)
Acne Rash	1/26 (3.8%)		1/0 (Infinity)
Rash	19/26 (73.1%)		19/0 (Infinity)
Vascular disorders
Hypertension	14/26 (53.8%)		14/0 (Infinity)
Hypotension	5/26 (19.2%)		5/0 (Infinity)

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.