Captopril Use on the Degree of Marrow Fibrosis in Bone Marrow Fibrosis/Myeloproliferative Neoplasms

NCT ID: NCT04629651

Last Updated: 2023-10-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-30
• Study Completion Date: 2024-10-31

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of captopril and evaluate the effectiveness captopril as measured by changes in the grade of bone marrow scar tissue. The change in spleen size by ultrasound will also be measured.

Detailed Description

Captopril is an investigational (experimental) drug that works by inhibiting the production of angiotensin II by blocking angiotensin converting enzyme. Reducing angiotensin II may reduce the bone marrow scar tissue in myelofibrosis. It is not approved by the Food and Drug Administration (FDA) for this indication. Participants in this study will be asked to have 2 bone marrow biopsies, a total of 3 blood samples, and fill out questionnaires asking about how you feel.

Conditions

Bone Marrow Fibrosis; Myeloproliferative Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Captopril

In phase I, Cohorts of 3 patients each will receive doses of captopril with a goal dose of 150mg total by mouth (PO) daily. Initial dose per patient will start at 12.5 mg daily, which will then be increased on weekly intervals as tolerated. To be administered per the intra-patient dose escalation scheme below

Phase I:

Day 0: 12.5mg/day Day 7: 12.5mg twice daily Day 14: 12.5mg three times daily Day 21: 25mg three times daily Day 28: 50mg three times daily

Phase II: The efficacy of captopril will be assessed in the Phase II portion. Captopril given at Maximum Tolerated Dose - bone marrow evaluation to be done at 6 months

Group Type: EXPERIMENTAL

Captopril

Intervention Type: DRUG

Oral, to be administered per the dose escalation scheme.

Interventions

Captopril

Oral, to be administered per the dose escalation scheme.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants must have histologically confirmed diagnosis of primary myelofibrosis (PMF), or post-polycythemia vera/essential thrombocythemia-MF (i.e. secondary MF) by 2016 WHO criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 -2
• Creatinine clearance >30 ml/minute
• Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study.
• Participants should be able to give voluntary informed written consent to participate in the study. Informed consent will be obtained prior to enrollment and before any study-related procedure is done that is not part of standard medical care, with the understanding that consent may be withdrawn by the participants any time without prejudice to future medical care.

Exclusion Criteria

• Completed hematopoietic cell transplant (HCT)
• Presence of >10% blasts in peripheral blood or on bone marrow examination
• Screening blood pressure(BP)parameters of systolic BP < 100 and diastolic BP < 60
• Splenic irradiation within 3 months prior to the first dose of captopril
• Prior ACE inhibitor, angiotensin II receptor antagonist, or aliskiren use within 12 months prior to trial enrolment
• Known allergy/hypersensitivity to ACE inhibitors
• Participants receiving any other investigational agents
• Pregnant or nursing participants - captopril is a risk category D and is excreted in breast milk
• Participants with creatinine clearance <30 ml/minute or on dialysis
• Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron Gerds, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic, Case Comprehensive Cancer Center

Locations

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE3920

Identifier Type: -

Identifier Source: org_study_id