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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Myeloproliferative Neoplasm; Bone Marrow Fibrosis

Treatments: Drug: Captopril

Study type: Interventional

Funder types: Other

Identifiers

NCT04629651

CASE3920

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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study-related procedure is done that is not part of standard medical care, with the understanding that consent may be withdrawn by the participants any time without prejudice to future medical care.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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Captopril

Experimental group

Description:

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

Treatment:

Drug: Captopril