NCT03746041

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Rochester · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The main objective of this study is to determine the safety and tolerability of combined abaloparatide + bevacizumab in MDS patients. This will be a single center, single arm, phase 1 trial in MDS patients. In cycle 1, patients will be treated with single-agent, subcutaneous (SQ) abaloparatide at a dose of 80 mcg/day for 28 days. This will enable the investigator to monitor for any potential toxicities of single-agent abaloparatide in the MDS patient population. Following cycle 1, patients will have a bone marrow aspirate to determine the impact of abaloparatide treatment on bone marrow stromal cell and hematopoietic cell populations. 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. At the end of study, patients will have a bone marrow aspirate and biopsy to assess disease response and to determine the impact of combined abaloparatide + bevacizumab on bone marrow stromal cell and hematopoietic cell populations. After completion of trial therapy, another bone marrow aspirate and biopsy will be done 3 months later to assess the delayed impact of treatment. The investigator has chosen a phase 1 trial design because this combination has not been previously evaluated for toxicity. Since safe and effective doses of both abaloparatide and bevacizumab have already been identified and both drugs are Food and Drug Administration (FDA)-approved, the investigator does not feel there is a need to dose-escalate. The investigator will carefully monitor for therapy-limiting toxicities (TLTs) throughout the course of the study and impose an early stopping rule for toxicity. To monitor for TLTs, patients will have laboratory tests weekly and clinic visits every other week throughout the course of the trial. TLT is defined in the protocol with grading of adverse events defined by the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Response will be defined according to 2006 IWG working criteria for MDS. Patients who have achieved complete remission (CR), partial remission (PR), marrow CR, and/or hematologic improvement at any time during the 7 month trial period will be considered responders. Eligible subjects will have a diagnosis of MDS or non-proliferative chronic myelomonocytic leukemia (CMML) based on 2016 world health organization (WHO) criteria, and associated signs of bone marrow failure characterized by at least some degree of cytopenia involving at least one cell line such as anemia, thrombocytopenia or leukopenia. Patients will not be allowed to receive concurrent active chemotherapy or growth factors.

Conditions

• Myelodysplastic Syndromes
• Chronic Myelomonocytic Leukemia

Interventions

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

Timeline

• Start date: 2019-02-14
• Primary completion: 2022-04-01
• Completion: 2022-06-06
• First posted: 2018-11-19
• Last updated: 2023-01-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study