A Phase I Pilot Study of Abaloparatide + Bevacizumab in Myelodysplastic Syndromes

Inclusion Criteria: * Age equal to or greater than 18 * Patients must have a documented diagnosis of MDS or non-proliferative chronic myelomonocytic leukemia (CMML) (WBC \< 12,000/mcL) according to World Health Organization (WHO) criteria (27) * Patients can be treatment-naïve or have received prior MDS-directed chemotherapy. * Treatment-naïve MDS patients (or those previously treated with growth factors alone) must have Revised International Prognostic Scoring System (IPSS-R) categories of Very Low-, Low- or Intermediate-risk disease (see Appendix A for Revised International Prognostic Scoring System for MDS). * MDS patients previously treated with disease-modifying chemotherapy (i.e. azacitidine, decitabine, lenalidomide, intensive chemotherapy, and/or an investigational agent) are eligible irrespective of IPSS-R score. * Patients must be off all non-transfusion therapy for MDS for 28 days prior to initiation of study treatment, including all types of growth factors. * Bone marrow biopsy (BMBx) within 30 days prior to first study treatment. * Cytopenia involving at least one cell line such as anemia, thrombocytopenia or leukopenia at the time of study enrollment. Cytopenias should be present on at least 2 different blood draws within 8 weeks of study enrollment. Definitions of cytopenias for the purposes of this study are as follows: * Anemia: Patients must be symptomatic in the opinion of the treating physician with a hemoglobin ≤ 10.0 g/dL * Thrombocytopenia: Platelet count \< 100,000/microliter * Neutropenia: Absolute neutrophil count \< 1000/microliter * ECOG Performance Status 0-2 * Adequate organ function as evidenced by: * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × the upper limit of normal (ULN). * Total bilirubin ≤2 mg/dL * Serum creatinine \<2 mg/dL, or creatinine clearance (calculated by the Cockcroft-Gault formula) ≤1.5 × ULN. * Urine dipstick for proteinuria \< 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours * International normalised ratio (INR) ≤1.5 and prothrombin time (PT) ≤ 1.5 x ULN * Women with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 30 days prior to enrollment into the study. * Females of childbearing potential and sexually active males must use effective contraception during the trial and for 6 months after the last dose of bevacizumab. * Written informed consent. Exclusion Criteria: * Bone marrow blasts equal to or greater than 20% * Patients actively receiving either abaloparatide, teriparatide or bisphosphonate therapy for other indications * Cumulative prior use of abaloparatide and/or any other parathyroid hormone analogs for \> 20 months * History of allogeneic stem cell transplant * Pregnant or breast feeding female subjects * Platelets \< 50,000/mm3 * Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrollment or anticipation of the need for major surgery during study treatment * Prior malignancy (excluding localized cervical carcinoma or cutaneous basal cell/squamous cell carcinoma) unless in remission for at least 2 years. * Concurrent malignancy (excluding localized cervical carcinoma or cutaneous basal cell/squamous cell carcinoma) * Need for aspirin at a dose of ≥ 325 mg/day; if aspirin can be safely stopped or dose dropped to \< 325 mg/day ≥ 10 days before the first dose of bevacizumab, then patient will remain eligible * Uncontrolled hypertension (blood pressures: systolic \> 150 mmHg and/or diastolic \> 100 mmHg) * Clinically significant cardiovascular disease present ≤6 months before enrollment as judged by the treating physician. Examples include: 1. Myocardial infarction 2. Unstable angina 3. Congestive heart failure NYHA Class ≥ II 4. Serious cardiac arrhythmia 5. Cerebrovascular accident and/or transient ischemic attack 6. Severe peripheral vascular disease (ischemic rest pain, non-healing wound or ulcer, or tissue loss) * Pulmonary embolus, deep venous thrombosis, or arterial thrombosis currently requiring anticoagulation * \< 10 days since prior anticoagulants * Non-healing wound, active peptic ulcer or bone fracture * History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrollment * Clinically significant hemorrhagic illness within the past 3 weeks * History of osteosarcoma * History of hyperparathyroidism * Elevated (\>ULN) serum calcium level * Patients at increased risk for osteosarcoma, including those with Paget's disease of bone, unexplained elevations of alkaline phosphatase, and/or prior external beam or implant radiation therapy involving the skeleton. * Psychiatric illness or social situation that would preclude study compliance * Patients unable to give informed consent or to be followed up adequately * Known hypersensitivity to a product from Chinese Hamster Ovary mammalian cell or to a recombinant humanized monoclonal antibody * Other investigational treatments within 28 days of the start of study therapy