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

NCT03746041 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 00003054
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the safety and tolerability of combined abaloparatide and bevacizumab in patients with Myelodysplastic Syndromes (MDS). A secondary objective is to determine the response to treatment (based on bone marrow and peripheral blood findings). A tertiary objective is to determine the impact of therapy on health-related quality of life (HRQOL) and patient-reported outcomes (PRO). A quaternary (scientific) objective is to determine the impact of treatment on both hematopoietic and stromal cell populations within the bone marrow of MDS patients.

Conditions

Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia

Keywords

Myelodysplastic syndromes; MDS; Chronic myelomonocytic leukemia; CMML; abaloparatide; bevacizumab; phase 1

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who experience a therapy-limiting Toxicity (TLT)

  Safety of this therapy will be based on subjects who complete at least two cycles, experiencing both study drugs for at least one cycle. TLT is defined as any serious AEs considered at least possibly due to abaloparatide and/or bevacizumab, occurring at any time from the initial dose of study treatment, with severity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.

  7 months

Secondary Outcomes (1)

• Proportion of patients who responded to therapy

  7 months

Study Arms (1)

abaloparatide and bevacizumab treatment

EXPERIMENTAL

In cycle 1, patients will be treated with single-agent, subcutaneous (SQ) abaloparatide at a dose of 80 mcg/day for 28 days. In cycles 2-4 (each cycle is 28 days), patients will be treated with SQ abaloparatide at a dose of 80 mcg/day and intravenous (IV) bevacizumab 5 mg/kg on days 1 and 15.

Drug: abaloparatide; Drug: bevacizumab

Interventions

abaloparatide DRUG

In cycle 1, patients will be treated with single-agent, subcutaneous (SQ) abaloparatide at a dose of 80 mcg/day for 28 days.

abaloparatide and bevacizumab treatment

bevacizumab DRUG

In cycles 2-4 (each cycle is 28 days), patients will be treated with SQ abaloparatide at a dose of 80 mcg/day and intravenous (IV) bevacizumab 5 mg/kg on days 1 and 15.

abaloparatide and bevacizumab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Myocardial infarction
• Unstable angina
• Congestive heart failure NYHA Class ≥ II

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14623, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

abaloparatide; Bevacizumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jason Mendler, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Hematology/Oncology

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 19, 2018
• Study Start: February 14, 2019
• Primary Completion: April 1, 2022
• Study Completion: June 6, 2022
• Last Updated: January 23, 2023

Record last verified: 2023-01

Locations

US (1)