Pasireotide in Prevention of GI Toxicity

This is an interventional treatment trial for Hematological Malignancies focused on measuring Allogeneic Stem Cell Transplantation, Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Acute Non-Lymphocytic Leukemia, Myelodysplastic Syndrome, Chronic Myeloid Leukemia, Lymphoma Read More

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.