Pasireotide in Prevention of GI Toxicity

• Status: Completed
• Trial end date: 2019-10-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Anthony Sung, MD
• Collaborator: Massachusetts General Hospital
• Treatments: Pasireotide; Somatostatin

Criteria

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.