- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03746041
A Phase I Pilot Study of Abaloparatide + Bevacizumab in Myelodysplastic Syndromes
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
Rochester, New York, United States, 14623
- University of Rochester
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- Myocardial infarction
- Unstable angina
- Congestive heart failure NYHA Class ≥ II
- Serious cardiac arrhythmia
- Cerebrovascular accident and/or transient ischemic attack
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: abaloparatide and bevacizumab treatment
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who experience a therapy-limiting Toxicity (TLT)
Time Frame: 7 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who responded to therapy
Time Frame: 7 months
|
In this study, patients who have achieved complete remission (CR), partial remission (PR), marrow CR, and/or hematologic improvement will be considered responders according to the International Working Group (IWG) Response Criteria and Modified IWG Response Criteria for Hematological Improvement.
The overall rate of response will be estimated among all subjects who received at least one dose of any study drug.
|
7 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jason Mendler, M.D., University of Rochester
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia
- Leukemia, Myeloid
- Syndrome
- Myelodysplastic Syndromes
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bone Density Conservation Agents
- Bevacizumab
- Abaloparatide
Other Study ID Numbers
- 00003054
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myelodysplastic Syndromes
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
National Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
GCP-Service International West GmbHSaint-Louis Hospital, Paris, France; University of Florence; Medical University... and other collaboratorsNot yet recruitingLow Risk Myelodysplastic SyndromesSpain, Poland, Italy, Germany, France
-
Dana-Farber Cancer InstituteCompletedMyelodysplastic Syndromes (MDS)United States
-
TJ Biopharma Co., Ltd.Recruiting
-
National Heart, Lung, and Blood Institute (NHLBI)National Cancer Institute (NCI)RecruitingMyelodysplastic Syndromes (MDS)United States, Israel
-
AbbVieCelgene; Genentech, Inc.CompletedMyelodysplastic Syndromes (MDS)United States, Australia, Germany
-
AbbVieGenentech, Inc.Active, not recruitingMyelodysplastic Syndromes (MDS)United States, Australia, Canada, France, Germany, Italy, United Kingdom
-
The First Affiliated Hospital with Nanjing Medical...UnknownMyelodysplastic Syndromes (MDS)China
-
Sumitomo Pharma America, Inc.TerminatedMyelodysplastic Syndromes (MDS)United States
Clinical Trials on abaloparatide
-
Radius Health, Inc.Medpace, Inc.Completed
-
Radius Health, Inc.CompletedPostmenopausal OsteoporosisUnited States, Poland, Denmark, Hungary, Puerto Rico
-
Radius Health, Inc.Nordic Bioscience A/SCompletedPost Menopausal OsteoporosisPoland, Denmark, United States, Estonia
-
Radius Health, Inc.Medpace, Inc.CompletedOsteoporosisUnited States
-
Radius Health, Inc.Completed
-
Radius Health, Inc.CompletedOsteoporosis | Postmenopausal OsteoporosisHong Kong, United States, Poland, Romania, Estonia, Czech Republic, Argentina, Brazil, Denmark, Lithuania
-
Hospital for Special Surgery, New YorkNew York University; Icahn School of Medicine at Mount Sinai; Weill Medical College... and other collaboratorsActive, not recruiting
-
Radius Health, Inc.CompletedOsteoporosis | Age Related Osteoporosis | Osteoporosis, Age-Related | Osteoporosis Localized to Spine | Osteoporosis Senile | Osteoporosis of VertebraeUnited States, Poland, Italy
-
University of Wisconsin, MadisonRadius Health, Inc.Active, not recruitingOsteoporosis | Arthroplasties, Knee ReplacementUnited States
-
Daniel HorwitzRadius Health, Inc.Not yet recruiting