Pasireotide in Prevention of GI Toxicity
Condition: Hematological Malignancies
MeSH terms: Hematologic Neoplasms
Intervention: Pasireotide
Intervention 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.
Intervention MeSH terms: Pasireotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Allogeneic Stem Cell Transplantation; Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Acute Non-Lymphocytic Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia; Lymphoma

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.
    

Eligibility 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.