Myelodysplastic SyndromesPhase 1NCT03746041
A Phase I Pilot Study of Abaloparatide + Bevacizumab in Myelodysplastic Syndromes
A Phase 1 study testing abaloparatide and bevacizumab in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by University of Rochester at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
- What is being tested?
- abaloparatide and bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2019to 6 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- abaloparatide, bevacizumab
- Keywords
- Myelodysplastic syndromes, MDS, Chronic myelomonocytic leukemia, CMML, abaloparatide, bevacizumab, phase 1
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
abaloparatideDrug
In cycle 1, patients will be treated with single-agent, subcutaneous (SQ) abaloparatide at a dose of 80 mcg/day for 28 days.
bevacizumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: abaloparatide; Drug: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 months
Secondary outcomes (1)
Proportion of patients who responded to therapy
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.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start14 Feb 2019
- Primary completion1 Apr 2022
- Study completion6 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Mendler, University of Rochester
- Investigators
- Jason Mendler, M.D., Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03746041
- Sponsor's protocol ID
- 00003054
- Status last verified
- Jan 2023
- First submitted
- 15 Nov 2018
- Last updated
- 23 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Pilot Study of Abaloparatide + Bevacizumab in Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT03746041
- Acronym / sponsor ID
- 00003054
- Keywords
- Myelodysplastic syndromes, MDS, Chronic myelomonocytic leukemia, CMML, abaloparatide, bevacizumab, phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 14 Feb 2019 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 6 Jun 2022 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| abaloparatide and bevacizumab treatment | Experimental | Drug: abaloparatide, Drug: bevacizumabIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
- 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.
Key exclusion criteria (31 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| abaloparatideIn cycle 1, patients will be treated with single-agent, subcutaneous (SQ) abaloparatide at a dose of 80 mcg/day for 28 days. | Drug | abaloparatide and bevacizumab treatment |
| bevacizumabIn 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 and bevacizumab treatment |
Primary outcome
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.
1 secondary outcome
Proportion of patients who responded to therapy
Time frame: 7 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Mendler, M.D. principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing abaloparatide and bevacizumab in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who experience a therapy-limiting Toxicity (TLT) (time frame: 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.